Skip to main content
Springer Nature Link
Log in

The Vascular Endothelium in Hypertension

  • Chapter
The Vascular Endothelium II

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 176/II))

Abstract

The vascular endothelium plays a fundamental role in the basal and dynamic regulation of the circulation. Thus, it has a crucial role in the pathogenesis of hypertension. A spectrum of vasoactive substances is synthesised in the endothelium; of these, nitric oxide (NO), prostacyclin (PGI2) and endothelin (ET)-1 are the most important. There is a continuous basal release of NO determining the tone of peripheral blood vessels. Systemic inhibition of NO synthesis or scavenging of NO through oxidative stress causes an increase in arterial blood pressure. Also, the renin-angiotensin-aldosterone system has a major role in hypertension as it has a direct vasoconstrictor effect and important interactions with oxygen free radicals and NO. Prostacyclin, in contrast to NO, does not contribute to the maintenance of basal vascular tone of conduit arteries, but its effect on platelets is most important. ET acts as the natural counterpart to endothelium-derived NO and has an arterial blood pressure-raising effect in man. Anti-hypertensive therapy lowers blood pressure and may influence these different mediators, thus influencing endothelial function. In summary, due to its position between the blood pressure and smooth muscle cells responsible for peripheral resistance, the endothelium is thought to be both victim and offender in arterial hypertension. The delicate balance of endothelium-derived factors is disturbed in hypertension. Specific anti-hypertensive and anti-oxidant treatment is able to restore this balance.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (Canada)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (Canada)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (Canada)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (Canada)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abassi ZA, Tate JE, Golomb E, Keiser HR (1992) Role of neutral endopeptidase in the metabolism of endothelin. Hypertension 20:89–95

    PubMed  CAS  Google Scholar 

  • Abassi ZA, Golomb E, Bridenbaugh R, Keiser HR (1993) Metabolism of endothelin-1 and big endothelin-1 by recombinant neutral endopeptidase EC.3.4.24.11. Br J Pharmacol 109:1024–1028

    PubMed  CAS  Google Scholar 

  • Anderson EA, Mark AL (1989) Flow-mediated and reflex changes in large peripheral artery tone in humans. Circulation 79:93–100

    PubMed  CAS  Google Scholar 

  • Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrage D, Lieberman EH, Ganz P, Creager MA, Yeung AC, Selwyn AP (1995) Close relation of endothelial function in the human coronary and peripheral circulation. J Am Coll Cardiol 26:1235–1241

    PubMed  CAS  Google Scholar 

  • Artigues-Varin C, Richard V, Renet S, Henry JP, Thuillez C (2002) Lack of impairment of nitric oxide-mediated responses in a rat model of high-renin hypertension. Clin Exp Pharmacol Physiol 29:26–31

    PubMed  CAS  Google Scholar 

  • Auch-Schwelk W, Katusic ZS, Vanhoutte PM (1989) Contractions to oxygen-derived free radicals are augmented in aorta of the spontaneously hypertensive rat. Hypertension 13:859–864

    PubMed  CAS  Google Scholar 

  • Barton M, Shaw S, d’Uscio LV, Moreau P, Lüscher TF (1997) Angiotensin II increases vascular and renal endothelin-1 and functional endothelin converting enzyme activity in vivo: role of ETA receptors for endothelin regulation. Biochem Biophys Res Commun 238: 861–865

    PubMed  CAS  Google Scholar 

  • Barton M, d’Uscio LV, Shaw S, Meyer P, Moreau P, Lüscher TF (1998) ET(A) receptor blockade prevents increased tissue endothelin-1, vascular hypertrophy, and endothelial dysfunction in salt-sensitive hypertension. Hypertension 31:499–504

    PubMed  CAS  Google Scholar 

  • Bhagat K, Vallance P (1997) Inflammatory cytokines impair endothelium-dependent dilatation in human veins in vivo. Circulation 96:3042–3047

    PubMed  CAS  Google Scholar 

  • Bhagat K, Moss R, Collier J, Vallance P (1996) Endothelial “stunning” following a brief exposure to endotoxin: a mechanism to link infection and infarction? Cardiovasc Res 32:822–829

    PubMed  CAS  Google Scholar 

  • Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE (1997) Common carotid intimamedia thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation 96:1432–1437

    PubMed  CAS  Google Scholar 

  • Boulanger C, Lüscher TF (1990) Release of endothelin from the porcine aorta. Inhibition of endothelium-derived nitric oxide. J Clin Invest 85:587–590

    PubMed  CAS  Google Scholar 

  • Boulanger CM, Tanner FC, Bea ML, Hahn AW, Werner A, Lüscher TF (1992) Oxidized low density lipoproteins induce mRNA expression and release of endothelin from human and porcine endothelium. Circ Res 70:1191–1197

    PubMed  CAS  Google Scholar 

  • Boulanger CM, Desta B, Clozel JP, Vanhoutte PM (1994) Chronic treatment with the CA2+ channel inhibitor RO 40-5967 potentiates endothelium-dependent relaxations in the aorta of the hypertensive salt sensitive Dahl rat. Blood Press 3:193–196

    PubMed  CAS  Google Scholar 

  • Bowman AJ, Chen CP, Ford GA (1994) Nitric oxidemediated venodilator effects of nebivolol. Br J Clin Pharmacol 38:199–204

    PubMed  CAS  Google Scholar 

  • Bragulat E, Larrousse M, Coca A, de la Sierra A (2003) Effect of long-term irbesartan treatment on endothelium-dependent vasodilation in essential hypertensive patients. Br J Biomed Sci 60:191–196

    PubMed  CAS  Google Scholar 

  • Brunner H, Cockcroft JR, Deanfield J, Donald A, Ferrannini E, Halcox J, Kiowski W, Lüscher TF, Mancia G, Natali A, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Spieker LE, Taddei S, Webb DJ (2005) Endothelial function and dysfunction. Part II. Association with cardiovascular risk factors and diseases. A statement by the Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension. J Hypertens 23:233–246

    PubMed  CAS  Google Scholar 

  • Calver A, Collier J, Moncada S, Vallance P (1992) Effect of local intra-arterial N G-monomethyl-L-arginine in patients with hypertension: the nitric oxide dilator mechanism appears abnormal. J Hypertens 10:1025–1031

    PubMed  CAS  Google Scholar 

  • Cardillo C, Kilcoyne CM, Cannon RO 3rd, Quyyumi AA, Panza JA (1997) Xanthine oxidase inhibition with oxypurinol improves endothelial vasodilator function in hypercholesterolemic but not in hypertensive patients. Hypertension 30:57–63

    PubMed  CAS  Google Scholar 

  • Cardillo C, Kilcoyne CM, Waclawiw M, Cannon RO 3rd, Panza JA (1999) Role of endothelin in the increased vascular tone of patients with essential hypertension. Hypertension 33:753–758

    PubMed  CAS  Google Scholar 

  • Cardillo C, Campia U, Iantorno M, Panza JA (2004) Enhanced vascular activity of endogenous endothelin-1 in obese hypertensive patients. Hypertension 43:36–40

    PubMed  CAS  Google Scholar 

  • Cervenka L, Horacek V, Vaneckova I, Hubacek JA, Oliverio MI, Coffman TM, Navar LG (2002) Essential role of AT1A receptor in the development of 2K1C hypertension. Hypertension 40:735–741

    PubMed  CAS  Google Scholar 

  • Chapleau MW, Hajduczok G, Abboud FM (1992) Suppression of baroreceptor discharge by endothelin at high carotid sinus pressure. Am J Physiol 263:R103–R108

    PubMed  CAS  Google Scholar 

  • Chen PY, Sanders PW (1991) L-Arginine abrogates salt-sensitive hypertension in Dahl/Rapp rats. J Clin Invest 88:1559–1567

    PubMed  CAS  Google Scholar 

  • Chen PY, Sanders PW (1993) Role of nitric oxide synthesis in salt-sensitive hypertension in Dahl/Rapp rats. Hypertension 22:812–818

    PubMed  CAS  Google Scholar 

  • Chen PY, St John PL, Kirk KA, Abrahamson DR, Sanders PW (1993) Hypertensive nephrosclerosis in the Dahl/Rapp rat. Initial sites of injury and effect of dietary L-arginine supplementation. Lab Invest 68:174–184

    PubMed  CAS  Google Scholar 

  • Chen R, Iwai M, Wu L, Suzuki J, Min LJ, Shiuchi T, Sugaya T, Liu HW, Cui TX, Horiuchi M (2003) Important role of nitric oxide in the effect of angiotensin-converting enzyme inhibitor imidapril on vascular injury. Hypertension 42:542–547

    PubMed  CAS  Google Scholar 

  • Chenevard R, Hurlimann D, Bechir M, Enseleit F, Spieker L, Hermann M, Riesen W, Gay S, Gay RE, Neidhart M, Michel B, Lüscher TF, Noll G, Ruschitzka F (2003) Selective COX-2 inhibition improves endothelial function in coronary artery disease. Circulation 107: 405–409

    PubMed  Google Scholar 

  • Cheng ZJ, Vapaatalo H, Mervaala E (2005) Angiotensin II and vascular inflammation. Med Sci Monit 11:RA194–RA205

    PubMed  CAS  Google Scholar 

  • Cockcroft JR, Chowienczyk PJ, Benjamin N, Ritter JM (1994) Preserved endothelium dependent vasodilatation in patients with essential hypertension. N Engl J Med 330: 1036–1040

    PubMed  CAS  Google Scholar 

  • Cockcroft JR, Chowienczyk PJ, Brett SE, Chen CP, Dupont AG, Van Nueten L, Wooding SJ, Ritter JM (1995) Nebivolol vasodilates human forearm vasculature: evidence for an L-arginine/NO-dependent mechanism. J Pharmacol Exp Ther 274:1067–1071

    PubMed  CAS  Google Scholar 

  • Cosentino F, Sill JC, Katusic ZS (1994) Role of superoxide anions in the mediation of endothelium-dependent contractions. Hypertension 23:223–235

    Google Scholar 

  • Cosentino F, Patton S, d’Uscio LV, Werner ER, Werner-Felmayer G, Moreau P, Malinski T, Lüscher TF (1998) Tetrahydrobiopterin alters superoxide and nitric oxide release in prehypertensive rats. J Clin Invest 101:1530–1537

    PubMed  CAS  Google Scholar 

  • Creager MA, Roddy MA (1994) Effect of captopril and enalapril on endothelial function in hypertensive patients. Hypertension 24:499–505

    PubMed  CAS  Google Scholar 

  • Creager MA, Roddy MA, Coleman SM, Dzau VJ (1992) The effect of ACE inhibition on endothelium-dependent vasodilation in hypertension. J Vasc Res 29:97

    Google Scholar 

  • d’Uscio LV, Shaw S, Barton M, Lüscher TF (1998) Losartan but not verapamil inhibits angiotensin II-induced tissue endothelin-1 increase: role of blood pressure and endothelial function. Hypertension 31:1305–1310

    PubMed  CAS  Google Scholar 

  • Dawes M, Brett SE, Chowienczyk PJ, Mant TG, Ritter JM (1999) The vasodilator action of nebivolol in forearm vasculature of subjects with essential hypertension. Br J Clin Pharmacol 48:460–463

    PubMed  CAS  Google Scholar 

  • De La Torre R, Casado A, Lopez-Fernandez E, Carrascosa D, Ramirez V, Saez J (1996) Overexpression of copper-zinc superoxide dismutase in trisomy 21. Experientia 52: 871–873

    Google Scholar 

  • Deanfield J, Donald A, Ferri C, Giannattasio C, Halcox J, Halligan S, Lerman A, Mancia G, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Schiffrin EL, Taddei S, Webb DJ (2005) Endothelial function and dysfunction. Part I. Methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. J Hypertens 23:7–17

    PubMed  CAS  Google Scholar 

  • Dechend R, Fiebler A, Lindschau C, Bischoff H, Muller D, Park JK, Dietz R, Haller H, Luft FC (2001) Modulating angiotensin II-induced inflammation by HMG Co-A reductase inhibition. Am J Hypertens 14:55S–61S

    PubMed  CAS  Google Scholar 

  • Demougeot C, Prigent-Tessier A, Marie C, Berthelot A (2005) Arginase inhibition reduces endothelial dysfunction and blood pressure rising in spontaneously hypertensive rats. J Hypertens 23:971–978

    PubMed  CAS  Google Scholar 

  • Deng AY, Rapp JP (1995) Locus for the inducible, but not a constitutive, nitric oxide synthase cosegregates with blood pressure in the Dahl salt-sensitive rat. JClin Invest 95:2170–2177

    CAS  Google Scholar 

  • Diederich D, Yang ZH, Bühler FR, Lüscher TF (1990) Impaired endothelium-dependent relaxations in hypertensive resistance arteries involve cyclooxygenase pathway. Am J Physiol 258:H445–H451

    PubMed  CAS  Google Scholar 

  • Dijkhorst-Oei LT, Stroes ES, Koomans HA, Rabelink TJ (1999) Acute simultaneous stimulation of nitric oxide and oxygen radicals by angiotensin II in humans in vivo. J Cardiovasc Pharmacol 33:420–424

    PubMed  CAS  Google Scholar 

  • Dohi Y, Thiel MA, Bühler FR, Lüscher TF (1990) Activation of endothelial L-arginine pathway in resistance arteries. Effect of age and hypertension. Hypertension 16:170–179

    PubMed  CAS  Google Scholar 

  • Dohi Y, Criscione L, Lüscher TF (1991) Renovascular hypertension impairs formation of endothelium-derived relaxing factors and sensitivity to endothelin-1 in resistance arteries. Br J Pharmacol 104:349–354

    PubMed  CAS  Google Scholar 

  • Dohi Y, Hahn AW, Boulanger CM, Bühler FR, Lüscher TF (1992) Endothelin stimulated by angiotensin II augments contractility of spontaneously hypertensive rat resistance arteries. Hypertension 19:131–137

    PubMed  CAS  Google Scholar 

  • Dohi Y, Criscione L, Pfeiffer K, Lüscher TF (1994) Angiotensin blockade or calcium antagonists improve endothelial dysfunction in hypertension: studies in perfused mesenteric resistance arteries. J Cardiovasc Pharmacol 24:372–379

    PubMed  CAS  Google Scholar 

  • Donckier JE, Hanet C, Berbinschi A, Galanti L, Robert A, Van Mechelen H, Pouleur H, Ketelslegers JM (1991) Cardiovascular and endocrine effects of endothelin-1 at pathophysiological and pharmacologicalplasma concentrations inconscious dogs. Circulation 84:2476–2484

    PubMed  CAS  Google Scholar 

  • Doucet J, Gonzalez W, Michel JB (1996) Endothelin antagonists in salt-dependent hypertension associated with renal insufficiency. J Cardiovasc Pharmacol 27:643–651

    PubMed  CAS  Google Scholar 

  • Duffy SJ, Gokce N, Holbrook M, Huang A, Frei B, Keaney JFJ, Vita JA (1999) Treatment of hypertension with ascorbic acid. Lancet 354:2048–2049

    PubMed  CAS  Google Scholar 

  • Edwards G, Dora KA, Gardener MJ, Garland CJ, Weston AH (1998) K+ is an endotheliumderived hyperpolarizing factor in rat arteries. Nature 396:269–272

    PubMed  CAS  Google Scholar 

  • Egashira K, Suzuki S, Hirooka Y, Kai H, Sugimachi M, Imaizumi T, Takeshita A (1995) Impaired endothelium-dependent vasodilation of large epicardial and resistance coronary arteries in patients with essential hypertension. Different responses to acetylcholine and substance P. Hypertension 25:201–206

    PubMed  CAS  Google Scholar 

  • Ferro CJ, Haynes WG, Hand MF, Webb DJ (2002) Forearm vasoconstriction to endothelin-1 is impaired, but constriction to sarafotoxin 6c and vasodilatation to BQ-123 unaltered, in patients with essential hypertension. Clin Sci (Lond) 103Suppl 48:53S–58S

    PubMed  CAS  Google Scholar 

  • Fichtlscherer S, Rosenberger G, Walter G, Breuer S, Dimmeler S, Zeiher AM (2000) Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation 102:1000–1006

    PubMed  CAS  Google Scholar 

  • Fleminger G, Bousso-Mittler D, Bdolah A, Kloog Y, Sokolovsky M (1989) Immunological and structural characterization of sarafotoxin/endothelin family of peptides. Biochem Biophys Res Commun 162:1317–1323

    PubMed  CAS  Google Scholar 

  • Forte P, Copland M, Smith LM, Milne E, Sutherland J, Benjamin N (1997) Basal nitric oxide synthesis in essential hypertension. Lancet 349:837–842

    PubMed  CAS  Google Scholar 

  • Fridovich I, Freeman B (1986) Antioxidant defenses in the lung. Annu Rev Physiol 48:693–702

    PubMed  CAS  Google Scholar 

  • Frielingsdorf J, Seiler C, Kaufmann P, Vassalli G, Suter T, Hess OM (1996) Normalization of abnormal coronary vasomotion by calcium antagonists in patients with hypertension. Circulation 93:1380–1387

    PubMed  CAS  Google Scholar 

  • Fujii K, Tominaga M, Ohmori S, Kobayashi K, Koga T, Takata Y, Fumjishima M (1992) Decreased endothelium-dependent hyperpolarizationto acetylcholine in smoothmuscle of the mesenteric artery of spontaneously hypertensive rats. Circ Res 70:660–669

    PubMed  CAS  Google Scholar 

  • Fukui T, Ishizaka N, Rajagopalan S, Laursen JB, Capers Qt, Taylor WR, Harrison DG, de Leon H, Wilcox JN, Griendling KK (1997) p22phox mRNA expression and NADPH oxidase activity are increased in aortas from hypertensive rats. Circ Res 80:45–51

    PubMed  CAS  Google Scholar 

  • Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376

    PubMed  CAS  Google Scholar 

  • Gardiner SM, Compton AM, Kemp PA, Bennett T (1990) Regional and cardiac haemodynamic responses to glyceryl trinitrate, acetylcholine, bradykinin and endothelin-1 in conscious rats: effects of NG-nitro-L-arginine methyl ester. Br J Pharmacol 101:632–639

    PubMed  CAS  Google Scholar 

  • Ghiadoni L, Taddei S, Virdis A, Sudano I, Di Legge V, Meola M, Di Venanzio L, Salvetti A (1998) Endothelial function and common carotid artery wall thickening in patients with essential hypertension. Hypertension 32:25–32

    PubMed  CAS  Google Scholar 

  • Ghiadoni L, Virdis A, Magagna A, Taddei S, Salvetti A (2000) Effect of the angiotensin II type 1 receptor blocker candesartan on endothelial function in patients with essential hypertension. Hypertension 35:501–506

    PubMed  CAS  Google Scholar 

  • Ghiadoni L, Magagna A, Versari D, Kardasz I, Huang Y, Taddei S, Salvetti A (2003) Different effect of antihypertensive drugs on conduit artery endothelial function. Hypertension 41:1281–1286

    PubMed  CAS  Google Scholar 

  • Goldblatt H, Lynch J, Hanzal RF, Summerville WW (1934) Studies on experimental hypertension, I: the production of persistent elevation of systolic blood pressure by means of renal ischemia. J Exp Med 59:347–379

    Google Scholar 

  • Grunfeld S, Hamilton CA, Mesaros S, McClain SW, Dominiczak AF, Bohr DF, Malinski T (1995) Role of superoxide in the depressed nitric oxide production by the endothelium of genetically hypertensive rats. Hypertension 26:854–857

    PubMed  CAS  Google Scholar 

  • Hayakawa H, Hirata Y, Suzuki E, Sugimoto T, Matsuoka H, Kikuchi K, Nagano T, Hirobe M, Sugimoto T (1993) Mechanisms for altered endothelium-dependent vasorelaxation in isolated kidneys from experimental hypertensive rats. Am J Physiol 264:H1535–H1541

    PubMed  CAS  Google Scholar 

  • Haynes WG, Webb DJ (1994) Contribution of endogenous generation of endothelin-1 to basal vascular tone. Lancet 344:852–854

    PubMed  CAS  Google Scholar 

  • Haynes WG, Ferro CJ, O’Kane KP, Somerville D, Lomax CC, Webb DJ (1996) Systemic endothelin receptor blockade decreases peripheral vascular resistance and blood pressure in humans. Circulation 93:1860–1870

    PubMed  CAS  Google Scholar 

  • Haynes WG, Ferro CJ, Webb DJ (1998) Bosentan in essential hypertension [letter; comment]. N Engl J Med 339:346; discussion 347

    PubMed  CAS  Google Scholar 

  • Hermann M, Camici G, Fratton A, Hurlimann D, Tanner FC, Hellermann JP, Fiedler M, Thiery J, Neidhart M, Gay RE, Gay S, Lüscherr TF, Ruschitzka F (2003) Differential effects of selective cyclooxygenase-2 inhibitors on endothelial function in salt-induced hypertension. Circulation 108:2308–2311

    PubMed  CAS  Google Scholar 

  • Hermann M, Shaw S, Kiss E, Camici G, Buhler N, Chenevard R, Lüscher TF, Grone HJ, Ruschitzka F (2005) Selective COX-2 inhibitors and renal injury in salt-sensitive hypertension. Hypertension 45:193–197

    PubMed  CAS  Google Scholar 

  • Hickey KA, Rubanyi G, Paul RJ, Highsmith RF (1985) Characterization of a coronary vasoconstrictor produced by cultured endothelial cells. Am J Physiol 248:C550–C556

    PubMed  CAS  Google Scholar 

  • Hieda HS, Gomez-Sanchez CE (1990) Hypoxia increases endothelin release in bovine endothelial cells in culture, but epinephrine, norepinephrine, serotonin, histamine and angiotensin II do not. Life Sci 47:247–251

    PubMed  CAS  Google Scholar 

  • Hingorani AD, Cross J, Kharbanda RK, Mullen MJ, Bhagat K, Taylor M, Donald AE, Palacios M, Griffin GE, Deanfield JE, MacAllister RJ, Vallance P (2000) Acute systemic inflammation impairs endothelium-dependent dilatation in humans. Circulation 102:994–999

    PubMed  CAS  Google Scholar 

  • Hirata Y, Hayakawa H, Suzuki E, Kimura K, Kikuchi K, Nagano T, Hirobe M, Omata M (1995) Direct measurements of endothelium-derived nitric oxide release by stimulation of endothelin receptors in rat kidney and its alteration in salt-induced hypertension. Circulation 91:1229–1235

    PubMed  CAS  Google Scholar 

  • Hirooka Y, Imaizumi T, Masaki H, Ando S, Harada S, Momohara M, Takeshita A (1992) Captopril improves impaired endothelium-dependent vasodilation in hypertensive patients. Hypertension 20:175–180

    PubMed  CAS  Google Scholar 

  • Hishikawa K, Oemar BS, Yang Z, Lüscher TF (1997) Pulsatile stretch stimulates superoxide production and activates nuclear factor-kappa B in human coronary smooth muscle. Circ Res 81:797–803

    PubMed  CAS  Google Scholar 

  • Hocher B, Rohmeiss P, Zart R, Diekmann F, Vogt V, Metz D, Fakhury M, Gretz N, Bauer C, Koppenhagen K, et al (1995) Significance of endothelin receptor subtypes in the kidneys of spontaneously hypertensive rats: renal and hemodynamic effects of endothelin receptor antagonists. J Cardiovasc Pharmacol 26Suppl 3:S470–S472

    PubMed  CAS  Google Scholar 

  • Hocher B, Rohmeiss P, Zart R, Diekmann F, Vogt V, Metz D, Fakhury M, Gretz N, Bauer C, Koppenhagen K, Neumayer HH, Distler A (1996) Function and expression of endothelin receptor subtypes in the kidneys of spontaneously hypertensive rats. Cardiovasc Res 31:499–510

    PubMed  CAS  Google Scholar 

  • Hocher B, George I, Rebstock J, Bauch A, Schwarz A, Neumayer HH, Bauer C (1999) Endothelin system-dependent cardiac remodeling in renovascular hypertension. Hypertension 33:816–822

    PubMed  Google Scholar 

  • Hu L, Manning RD Jr (1995) Role of nitric oxide in regulation of long-term pressurenatriuresis relationship in Dahl rats. Am J Physiol 268:H2375–H2383

    PubMed  CAS  Google Scholar 

  • Ikeda Y, Saito K, Kim JI, Yokoyama M (1995) Nitric oxide synthase isoform activities in kidney of Dahl salt-sensitive rats. Hypertension 26:1030–1034

    PubMed  CAS  Google Scholar 

  • Ikegawa R, Matsumura Y, Tsukahara Y, Takaoka M, Morimoto S (1990) Phosphoramidon, a metalloproteinase inhibitor, suppresses the secretion of endothelin-1 from cultured endothelial cells by inhibiting a big endothelin-1 converting enzyme. Biochem Biophys Res Commun 171:669–675

    PubMed  CAS  Google Scholar 

  • Inoue A, Yanagisawa M, Kimura S, Kasuya Y, Miyauchi T, Goto K, Masaki T (1989a) The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci U S A 86:2863–2867

    PubMed  CAS  Google Scholar 

  • Inoue A, Yanagisawa M, Takuwa Y, Mitsui Y, Kobayashi M, Masaki T (1989b) The human preproendothelin-1 gene. Complete nucleotide sequence and regulation of expression. J Biol Chem 264:14954–14959

    PubMed  CAS  Google Scholar 

  • Ito H, Hirata Y, Hiroe M, Tsujino M, Adachi S, Takamoto T, Nitta M, Taniguchi K, Marumo F (1991) ET-1 induces hypertrophy with enhanced expression of muscle specific genes in cultured neonatal rat cardiomyocytes. Circ Res 69:209–215

    PubMed  CAS  Google Scholar 

  • Jameson M, Dai FX, Lüscher T, Skopec J, Diederich A, Diederich D (1993) Endotheliumderived contracting factors in resistance arteries of young spontaneously hypertensive rats before development of overt hypertension. Hypertension 21:280–288

    PubMed  CAS  Google Scholar 

  • Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C, Lüscher TF (1995a) Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation 91:1314–1319

    PubMed  CAS  Google Scholar 

  • Joannides R, Richard V, Haefeli WE, Linder L, Lüscher TF, Thuillez C (1995b) Role of basal and stimulated release of nitric oxide in the regulation of radial artery caliber in humans. Hypertension 26:327–331

    PubMed  CAS  Google Scholar 

  • Kakoki M, Hirata Y, Hayakawa H, Tojo A, Nagata D, Suzuki E, Kimura K, Goto A, Kikuchi K, Nagano T, Omata M (1999) Effects of hypertension, diabetes mellitus, and hypercholesterolemia on endothelin type B receptor-mediated nitric oxide release from rat kidney. Circulation 99:1242–1248

    PubMed  CAS  Google Scholar 

  • Kannan H, Tanaka H, Ueta Y, Hayashida Y, Kunitake T, Yamashita H (1994) Effectsof centrally administered endothelin-3 on renal sympathetic nerve activity and renal blood flow in conscious rats. J Auton Nerv Syst 49:105–113

    PubMed  CAS  Google Scholar 

  • Kannel WB, Gordon T, Offutt D (1969) Left ventricular hypertrophy by electrocardiogram. Prevalence, incidence, and mortality in the Framingham study. Ann Intern Med 71: 89–105

    PubMed  CAS  Google Scholar 

  • Kanse SM, Takahashi K, Lam HC, Rees A, Warren JB, Porta M, Molinatti P, Ghatei M, Bloom SR (1991) Cytokine stimulated endothelin release from endothelial cells. Life Sci 48:1379–1384

    PubMed  CAS  Google Scholar 

  • Katusic ZS, Vanhoutte PM (1989) Superoxide anion is an endothelium-derived contracting factor. Am J Physiol 257:H33–H37

    PubMed  CAS  Google Scholar 

  • Katusic ZS, Schugel J, Cosentino F, Vanhoutte PM (1993) Endothelium-dependent contractions to oxygen-derived free radicals in the canine basilar artery. Am J Physiol 264:H859–H864

    PubMed  CAS  Google Scholar 

  • Kelm M, Feelisch M, Krebber T, Motz W, Strauer BE (1992) The role of nitric oxide in the regulation of coronary vascular resistance in arterial hypertension: comparison of normotensive and spontaneously hypertensive rats. J Cardiovasc Pharmacol 20: S183–S186

    PubMed  CAS  Google Scholar 

  • Kerr S, Brosnan MJ, McIntyre M, Reid JL, Dominiczak AF, Hamilton CA (1999) Superoxide anion production is increased in a model of genetic hypertension: role of the endothelium. Hypertension 33:1353–1358

    PubMed  CAS  Google Scholar 

  • Kiely DG, Cargill RI, Struthers AD, Lipworth BJ (1997) Cardiopulmonary effects of endothelin-1 in man. Cardiovasc Res 33:378–386

    PubMed  CAS  Google Scholar 

  • Kloog Y, Ambar I, Sokolovsky M, Kochva E, Wollberg Z, Bdolah A (1988) Sarafotoxin, a novel vasoconstrictor peptide: phosphoinositide hydrolysis in rat heart and brain. Science 242:268–270

    PubMed  CAS  Google Scholar 

  • Knuepfer MM, Han SP, Trapani AJ, Fok KF, Westfall TC (1989) Regional hemodynamic and baroreflex effects of endothelin in rats. Am J Physiol 257:H918–H926

    PubMed  CAS  Google Scholar 

  • Kohno M, Murakawa K, Yokokawa K, Yasunari K, Horio T, Kurihara N, Takeda T (1989) Production of endothelin by cultured porcine endothelial cells: modulation by adrenaline. J Hypertens Suppl 7:S130–S131

    PubMed  CAS  Google Scholar 

  • Koller A, Kaley G (1990) Prostaglandins mediate arteriolar dilation to increased blood flow velocity in skeletal muscle microcirculation. Circ Res 67:529–534

    PubMed  CAS  Google Scholar 

  • Kontos HA, Wei EP, Ellis EF, Jenkins LW, Povlishock JT, Rowe GT, Hess ML (1985) Appearance of superoxide anion radical in cerebral extracellular space during increased prostaglandin synthesis in cats. Circ Res 57:142–151

    PubMed  CAS  Google Scholar 

  • Kourembanas S, Marsden PA, McQuillan LP, Faller DV (1991) Hypoxia induces endothelin gene expression and secretion in cultured human endothelium. J Clin Invest 88:1054–1057

    PubMed  CAS  Google Scholar 

  • Küng CF, Lüscher TF (1995) Different mechanisms of endothelial dysfunction with aging and hypertension in rat aorta. Hypertension 25:194–200

    PubMed  Google Scholar 

  • Lariviere R, Day R, Schiffrin EL (1993a) Increased expression of endothelin-1 gene in blood vessels of deoxycorticosterone acetate-salt hypertensive rats. Hypertension 21:916–920

    PubMed  CAS  Google Scholar 

  • Lariviere R, Thibault G, Schiffrin EL (1993b) Increased endothelin-1 content in blood vessels of deoxycorticosterone acetate-salt hypertensive but not in spontaneously hypertensive rats. Hypertension 21:294–300

    PubMed  CAS  Google Scholar 

  • Lariviere R, Sventek P, Schiffrin EL (1995) Expression of endothelin-1 gene in blood vessels of adult spontaneously hypertensive rats. Life Sci 56:1889–1896

    PubMed  CAS  Google Scholar 

  • Laursen JB, Rajagopalan S, Galis Z, Tarpey M, Freeman BA, Harrison DG (1997) Role of superoxide in angiotensin II-induced but not catecholamine-induced hypertension. Circulation 95:588–593

    PubMed  CAS  Google Scholar 

  • Lee J, Choi KC, Yeum CH, Kim W, Yoo K, Park JW, Yoon PJ (1995) Impairment of endothelium-dependent vasorelaxation in chronic two-kidney, one clip hypertensive rats. Nephrol Dial Transplant 10:619–623

    PubMed  CAS  Google Scholar 

  • Lepori M, Sartori C, Trueb L, Owlya R, Nicod P, Scherrer U (1998) Haemodynamic and sympathetic effects of inhibition of nitric oxide synthase by systemic infusion of N(G)-monomethyl-L-arginine into humans are dose dependent. J Hypertens 16:519–523

    PubMed  CAS  Google Scholar 

  • Levanon D, Lieman-Hurwitz J, Dafni N, Wigderson M, Sherman L, Bernstein Y, Laver-Rudich Z, Danciger E, Stein O, Groner Y (1985) Architecture and anatomy of the chromosomal locus in human chromosome 21 encoding the Cu/Zn superoxide dismutase. EMBO J 4:77–84

    PubMed  CAS  Google Scholar 

  • Lewis SJ, Ohta H, Machado B, Bates JN, Talman WT (1991) Microinjection of S-nitrosocysteine into the nucleus tractus solitarii decreases arterial pressure and heart rate via activation of soluble guanylate cyclase. Eur J Pharmacol 202:135–136

    PubMed  CAS  Google Scholar 

  • Li JS, Lariviere R, Schiffrin EL (1994) Effect of a nonselective endothelin antagonist on vascular remodeling in deoxycorticosterone acetate-salt hypertensive rats. Evidence for a role of endothelin in vascular hypertrophy. Hypertension 24:183–188

    PubMed  CAS  Google Scholar 

  • Li L, Fink GD, Watts SW, Northcott CA, Galligan JJ, Pagano PJ, Chen AF (2003) Endothelin-1 increases vascular superoxide via endothelin(A)-NADPH oxidase pathway in low-renin hypertension. Circulation 107:1053–1058

    PubMed  CAS  Google Scholar 

  • Linder L, Kiowski W, Bühler FR, Lüscher TF (1990) Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension. Circulation 81:1762–1767

    PubMed  CAS  Google Scholar 

  • Lüscher TF (1990) Imbalance of endothelium-derived relaxing and contracting factors. A new concept in hypertension? Am J Hypertens 317:317–330

    Google Scholar 

  • Lüscher TF, Noll G (1997) Endothelium-derived vasoactive substances. In: Braunwald E (ed) Heart disease, 5 edn. WB Saunders, Philadelphia, pp 1165

    Google Scholar 

  • Lüscher TF, Vanhoutte PM (1986) Endothelium-dependent contractions to acetylcholine in the aorta of the spontaneously hypertensive rat. Hypertension 8:344–348

    PubMed  Google Scholar 

  • Lüscher TF, Vanhoutte PM (1990) The endothelium: modulator of cardiovascular function. CRC Press, Boca Ranton

    Google Scholar 

  • Lüscher TF, Romero JC, Vanhoutte PM (1986) Bioassay of endothelium-derived substances in the aorta of normotensive and spontaneously hypertensive rats. J Hypertens 4Suppl 6:81

    Google Scholar 

  • Lüscher TF, Raij L, Vanhoutte PM (1987a) Endothelium-dependent vascular responses in normotensive and hypertensive Dahl rats. Hypertension 9:157–163

    PubMed  Google Scholar 

  • Lüscher TF, Vanhoutte PM, Raij L (1987b) Antihypertensive treatment normalizes decreased endothelium-dependent relaxations in rats with salt-induced hypertension. Hypertension 9Suppl 3:193–197

    Google Scholar 

  • Lüscher TF, Yang Z, Tschudi M, Von SL, Stulz P, Boulanger C, Siebenmann R, Turina M, Bühler FR (1990) Interaction between endothelin-1 and endothelium-derived relaxing factor in human arteries and veins. Circ Res 66:1088–1094

    PubMed  Google Scholar 

  • Lyons D, Webster J, Benjamin N (1994) The effect of antihypertensive therapy on responsiveness to local intra-arterial NG-monomethyl-L-arginine in patients with essential hypertension. J Hypertens 12:1047–1052

    PubMed  CAS  Google Scholar 

  • Lysko PG, Feuerstein G, Pullen M, Wu HL, Nambi P (1991) Identification of endothelin receptors in cultured cerebellar neurons. Neuropeptides 18:83–86

    PubMed  CAS  Google Scholar 

  • Machha A, Mustafa MR (2005) Chronic treatment with flavonoids prevents endothelial dysfunction in spontaneously hypertensive rat aorta. J Cardiovasc Pharmacol 46:36–40

    PubMed  CAS  Google Scholar 

  • Maeso R, Rodrigo E, Munoz-Garcia R, Navarro-Cid J, Ruilope LM, Cachofeiro V, Lahera V (1998) Chronic treatment with losartan ameliorates vascular dysfunction induced by aging in spontaneously hypertensive rats. J Hypertens 16:665–672

    PubMed  CAS  Google Scholar 

  • Matsuoka H, Itoh S, Kimoto M, Kohno K, Tamai O, Wada Y, Yasukawa H, Iwami G, Okuda S, Imaizumi T (1997) Asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in experimental hypertension. Hypertension 29:242–247

    PubMed  CAS  Google Scholar 

  • McAllister AS, Atkinson AB, Johnston GD, Hadden DR, Bell PM, McCance DR (1999) Basal nitric oxide production is impaired in offspring of patients with essential hypertension. Clin Sci (Lond) 97:141–147

    PubMed  CAS  Google Scholar 

  • McIntyre M, Hamilton CA, Rees DD, Reid JL, Dominiczak AF (1997) Sex differences in the abundance of endothelial nitric oxide in a model of genetic hypertension. Hypertension 30:1517–1524

    PubMed  CAS  Google Scholar 

  • Millgard J, Lind L (1998) Acute hypertension impairs endothelium-dependent vasodilation. Clin Sci (Lond) 94:601–607

    PubMed  CAS  Google Scholar 

  • Millgard J, Hagg A, Sarabi M, Lind L (1998) Captopril, but not nifedipine, improves endothelium-dependent vasodilation in hypertensive patients. J Hum Hypertens 12: 511–516

    PubMed  CAS  Google Scholar 

  • Miyamori I, Takeda Y, Yoneda T, Iki K, Takeda R (1991) Interleukin-2 enhances the release of endothelin-1 from the rat mesenteric artery. Life Sci 49:1295–1300

    PubMed  CAS  Google Scholar 

  • Miyauchi T, Ishikawa T, Tomobe Y, Yanagisawa M, Kimura S, Sugishita Y, Ito I, Goto K, Masaki T (1989) Characteristics of pressor response to endothelin in spontaneously hypertensive and Wistar-Kyoto rats. Hypertension 14:427–434

    PubMed  CAS  Google Scholar 

  • Miyauchi T, Yanagisawa M, Iida K, Ajisaka R, Suzuki N, Fujino M, Goto K, Masaki T, Sugishita Y (1992) Age-and sex-related variation of plasma endothelin-1 concentration in normal and hypertensive subjects. Am Heart J 123:1092–1093

    PubMed  CAS  Google Scholar 

  • Moncada S, Gryglewski R, Bunting S, Vane JR (1976) An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263:663–665

    PubMed  CAS  Google Scholar 

  • Moreau P, d’Uscio LV, Shaw S, Takase H, Barton M, Lüscher TF (1997) Angiotensin II increases tissue endothelin and induces vascular hypertrophy: reversal by ET(A)-receptor antagonist. Circulation 96:1593–1597

    PubMed  CAS  Google Scholar 

  • Morrison RA, McGrath A, Davidson G, Brown JJ, Murray GD, Lever AF (1996) Low blood pressure in Down’s syndrome, a link with Alzheimer’s disease? Hypertension 28:569–575

    PubMed  CAS  Google Scholar 

  • Mosqueda-Garcia R, Appalsamy M, Fernandez-Violante R, Hamakubo T (1998) Modulatory effects of endothelin on baroreflex activation in the nucleus of the solitary tract. Eur J Pharmacol 351:203–207

    PubMed  CAS  Google Scholar 

  • Nakamoto H, Suzuki H, Murakami M, Kageyama Y, Naitoh M, Sakamaki Y, Ohishi A, Saruta T (1991) Different effects of low and high doses of endothelin on haemodynamics and hormones in the normotensive conscious dog. J Hypertens 9:337–344

    PubMed  CAS  Google Scholar 

  • Nakazono K, Watanabe N, Matsuno K, Sasaki J, Sato T, Inoue M (1991) Does superoxide underlie the pathogenesis of hypertension? Proc Natl Acad Sci U S A 88:10045–10048

    PubMed  CAS  Google Scholar 

  • Nambi P, Pullen M, Feuerstein G (1990) Identification of endothelin receptors in various regions of rat brain. Neuropeptides 16:195–199

    PubMed  CAS  Google Scholar 

  • Nava E, Noll G, Lüscher TF (1995) Increased activity of constitutive nitric oxide synthase in cardiac endothelium in spontaneous hypertension. Circulation 91:2310–2313

    PubMed  CAS  Google Scholar 

  • Nava E, Farre AL, Moreno C, Casado S, Moreau P, Cosentino F, Lüscher TF (1998) Alterations to the nitric oxide pathway in the spontaneously hypertensive rat. J Hypertens 16:609–615

    PubMed  CAS  Google Scholar 

  • Ni Z, Oveisi F, Vaziri ND (1999) Nitric oxide synthase isotype expression in salt-sensitive and salt-resistant Dahl rats. Hypertension 34:552–557

    PubMed  CAS  Google Scholar 

  • Nicaud V, Poirier O, Behague I, Herrmann SM, Mallet C, Troesch A, Bouyer J, Evans A, Luc G, Ruidavets JB, Arveiler D, Bingham A, Tiret L, Cambien F (1999) Polymorphisms of the endothelin-A and-B receptor genes in relation to blood pressure and myocardial infarction: the Etude Cas-Temoins sur l’Infarctus du Myocarde (ECTIM) Study. Am J Hypertens 12:304–310

    PubMed  CAS  Google Scholar 

  • Nohria A, Garrett L, Johnson W, Kinlay S, Ganz P, Creager MA (2003) Endothelin-1 and vascular tone in subjects with atherogenic risk factors. Hypertension 42:43–48

    PubMed  CAS  Google Scholar 

  • Noll G, Lang MG, Tschudi MR, Ganten D, Lüscher TF (1997) Endothelial vasoconstrictor prostanoids modulate contractions to acetylcholine and ANG II in Ren-2 rats. Am J Physiol 272:H493–H500

    PubMed  CAS  Google Scholar 

  • O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr (1999) Carotidartery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 340:14–22

    PubMed  CAS  Google Scholar 

  • Ohnaka K, Takayanagi R, Nishikawa M, Haji M, Nawata H (1993) Purification and characterization of a phosphoramidon-sensitive endothelin-converting enzyme in porcine aortic endothelium. J Biol Chem 268:26759–26766

    PubMed  CAS  Google Scholar 

  • Ohta K, Hirata Y, Imai T, Kanno K, Emori T, Shichiri M, Marumo F (1990) Cytokineinduced release of endothelin-1 fromporcine renal epithelial cell line. Biochem Biophys Res Commun 169:578–584

    PubMed  CAS  Google Scholar 

  • Okahara K, Sun B, Kambayashi J (1998) Upregulation of prostacyclin synthesis-related gene expression by shear stress in vascular endothelial cells. Arterioscler Thromb Vasc Biol 18:1922–1926

    PubMed  CAS  Google Scholar 

  • Palmer RM, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526

    PubMed  CAS  Google Scholar 

  • Palmer RM, Ashton DS, Moncada S (1988a) Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333:664–666

    PubMed  CAS  Google Scholar 

  • Palmer RMJ, Rees DD, Ashton DS, Moncada S (1988b) L-Arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun 153:1251–1256

    PubMed  CAS  Google Scholar 

  • Palmer RM, Bridge L, Foxwell NA, Moncada S (1992) The role of nitric oxide in endothelial cell damage and its inhibition by glucocorticoids. Br J Pharmacol 105:11–12

    PubMed  CAS  Google Scholar 

  • Panza JA, Quyyumi AA, Brush JJ, Epstein SE (1990) Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 323:22–27

    PubMed  CAS  Google Scholar 

  • Panza JA, Casino PR, Badar DM, Quyyumi AA (1993a) Effect of increased availability of endothelium-derived nitric oxide precursor on endothelium-dependent vascular relaxation in normal subjects and in patients with essential hypertension. Circulation 87:1475–1481

    PubMed  CAS  Google Scholar 

  • Panza JA, Casino PR, Kilcoyne CM, Quyyumi AA (1993b) Role of endothelium-derived nitric oxide in the abnormal endothelium-dependent vascular relaxation of patients with essential hypertension. Circulation 87:1468–1474

    PubMed  CAS  Google Scholar 

  • Panza JA, Quyyumi AA, Callahan TS, Epstein SE (1993c) Effect of antihypertensive treatment on endothelium-dependent vascular relaxation in patients with essential hypertension. J Am Coll Cardiol 21:1145–1151

    PubMed  CAS  Google Scholar 

  • Panza JA, Casino PR, Kilcoyne CM, Quyyumi AA (1994) Impaired endothelium-dependent vasodilation in patients with essential hypertension: evidence that the abnormality is not at the muscarinic receptor level. J Am Coll Cardiol 23:1610–1616

    PubMed  CAS  Google Scholar 

  • Panza JA, Garcia CE, Kilcoyne CM, Quyyumi AA, Cannon RO 3rd (1995) Impaired endothelium-dependent vasodilation in patients with essential hypertension. Evidence that nitric oxide abnormality is not localized to a single signal transduction pathway. Circulation 91:1732–1738

    PubMed  CAS  Google Scholar 

  • Perticone F, Ceravolo R, Maio R, Ventura G, Zingone A, Perrotti N, Mattioli PL (1998) Angiotensin-converting enzyme gene polymorphism is associated with endotheliumdependent vasodilation in never treated hypertensive patients. Hypertension 31:900–905

    PubMed  CAS  Google Scholar 

  • Perticone F, Maio R, Ceravolo R, Cosco C, Cloro C, Mattioli PL (1999a) Relationship between left ventricular mass and endothelium-dependent vasodilation in never-treated hypertensive patients. Circulation 99:1991–1996

    PubMed  CAS  Google Scholar 

  • Perticone F, Ceravolo R, Maio R, Ventura G, Iacopino S, Cuda G, Mastroroberto P, Chello M, Mattioli PL (1999b) Calcium antagonist isradipine improves abnormal endotheliumdependent vasodilation in never treated hypertensive patients. Cardiovasc Res 41:299–306

    PubMed  CAS  Google Scholar 

  • Pohl U, Holtz J, Busse R, Bassenge E (1986) Crucial role of endothelium in the vasodilator response to increased flow in vivo. Hypertension 8:37–44

    PubMed  CAS  Google Scholar 

  • Radomski MW, Palmer RM, Moncada S (1987) Comparative pharmacology of endotheliumderived relaxing factor, nitric oxide and prostacyclin in platelets. Br J Pharmacol 92:181–187

    PubMed  CAS  Google Scholar 

  • Rajagopalan S, Kurz S, Munzel T, Tarpey M, Freeman BA, Griendling KK, Harrison DG (1996) Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 97:1916–1923

    PubMed  CAS  Google Scholar 

  • Richard V, Tanner FC, Tschudi M, Lüscher TF (1990) Different activation of L-arginine pathway by bradykinin, serotonin, and clonidine in coronary arteries. Am J Physiol 259:H1433–H1439

    PubMed  CAS  Google Scholar 

  • Rodrigo E, Maeso R, Munoz-Garcia R, Navarro-Cid J, Ruilope LM, Cachofeiro V, Lahera V (1997) Endothelial dysfunction in spontaneously hypertensive rats: consequences of chronic treatment with losartan or captopril. J Hypertens 15:613–618

    PubMed  CAS  Google Scholar 

  • Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340:115–126

    PubMed  CAS  Google Scholar 

  • Rossi GP, Albertin G, Franchin E, Sacchetto A, Cesari M, Palu G, Pessina AC (1995) Expression of the endothelin-converting enzyme gene in human tissues. Biochem Biophys Res Commun 211:249–253

    PubMed  CAS  Google Scholar 

  • Rossi GP, Colonna S, Pavan E, Albertin G, Della Rocca F, Gerosa G, Casarotto D, Sartore S, Pauletto P, Pessina AC (1999) Endothelin-1 and its mRNA in the wall layers of human arteries ex vivo. Circulation 99:1147–1155

    PubMed  CAS  Google Scholar 

  • Rossi GP, Ganzaroli C, Cesari M, Maresca A, Plebani M, Nussdorfer GG, Pessina AC (2003) Endothelin receptor blockade lowers plasma aldosterone levels via different mechanisms in primary aldosteronism and high-to-normal renin hypertension. Cardiovasc Res 57:277–283

    PubMed  CAS  Google Scholar 

  • Rubanyi GM, Vanhoutte PM (1986) Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor. Am J Physiol 250:H822–H827

    PubMed  CAS  Google Scholar 

  • Rubanyi GM, Romero JC, Vanhoutte PM (1986) Flow-induced release of endotheliumderived relaxing factor. Am J Physiol 250:H1145–H1149

    PubMed  CAS  Google Scholar 

  • Rudd MA, Trolliet M, Hope S, Scribner AW, Daumerie G, Toolan G, Cloutier T, Loscalzo J (1999) Salt-induced hypertension in Dahl salt-resistant and salt-sensitive rats with NOS II inhibition. Am J Physiol 277:H732–H739

    PubMed  CAS  Google Scholar 

  • Saito Y, Nakao K, Mukoyama M, Imura H (1990) Increased plasma endothelin level in patients with essential hypertension [letter]. N Engl J Med 322:205

    PubMed  CAS  Google Scholar 

  • Sartori C, Lepori M, Scherrer U (2005) Interaction between nitric oxide and the cholinergic and sympathetic nervous system in cardiovascular control in humans. Pharmacol Ther 106:209–220

    PubMed  CAS  Google Scholar 

  • Schiffrin EL (2005) Vascular endothelin in hypertension. Vascul Pharmacol 43:19–29

    PubMed  CAS  Google Scholar 

  • Schiffrin EL, Deng LY (1996) Structure and function of resistance arteries of hypertensive patients treated with a beta-blocker or a calcium channel antagonist. J Hypertens 14:1247–1255

    PubMed  CAS  Google Scholar 

  • Schiffrin EL, Lariviere R, Li JS, Sventek P, Touyz RM (1995a) Deoxycorticosterone acetate plus salt induces overexpression of vascular endothelin-1 and severe vascular hypertrophy in spontaneously hypertensive rats. Hypertension 25:769–773

    PubMed  CAS  Google Scholar 

  • Schiffrin EL, Deng LY, Larochelle P (1995b) Progressive improvement in the structure of resistance arteries of hypertensive patients after 2 years of treatment with an angiotensin I-converting enzyme inhibitor. Comparison with effects of a beta-blocker. Am J Hypertens 8:229–236

    PubMed  CAS  Google Scholar 

  • Scotland RS, Madhani M, Chauhan S, Moncada S, Andresen J, Nilsson H, Hobbs AJ, Ahluwalia A (2005) Investigation of vascular responses in endothelial nitric oxide synthase/cyclooxygenase-1 double-knockout mice: key role for endothelium-derived hyperpolarizing factor in the regulation of blood pressure in vivo. Circulation 111:796–803

    PubMed  CAS  Google Scholar 

  • Sekiguchi F, Yanamoto A, Sunano S (2004) Superoxide dismutase reduces the impairment of endothelium-dependent relaxation in the spontaneously hypertensive rat aorta. J Smooth Muscle Res 40:65–74

    PubMed  Google Scholar 

  • Sharma P, Hingorani A, Jia H, Hopper R, Brown MJ (1999) Quantitative association between a newly identified molecular variant in the endothelin-2 gene and human essential hypertension. J Hypertens 17:1281–1287

    PubMed  CAS  Google Scholar 

  • Shimada K, Takahashi M, Tanzawa K (1994) Cloning and functional expression of endothelin-converting enzyme from rat endothelial cells. J Biol Chem 269:18275–18278

    PubMed  CAS  Google Scholar 

  • Shimokawa H, Yasutake H, Fujii K, Owada MK, Nakaike R, Fukumoto Y, Takayanagi T, Nagao T, Egashira K, Fujishima M, Takeshita A (1996) The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation. J Cardiovasc Pharmacol 28:703–711

    PubMed  CAS  Google Scholar 

  • Shirakami G, Nakao K, Saito Y, Magaribuchi T, Jougasaki M, Mukoyama M, Arai H, Hosoda K, Suga S, Ogawa Y, et al (1991) Acute pulmonary alveolar hypoxia increases lung and plasma endothelin-1 levels in conscious rats. Life Sci 48:969–976

    PubMed  CAS  Google Scholar 

  • Simchon S, Manger W, Blumberg G, Brensilver J, Cortell S (1996) Impaired renal vasodilation and urinary cGMP excretion in Dahl salt-sensitive rats. Hypertension 27:653–657

    PubMed  CAS  Google Scholar 

  • Sorensen SS (1991) Radio-immunoassay of endothelin in human plasma. Scand J Clin Lab Invest 51:615–623

    PubMed  CAS  Google Scholar 

  • Sorensen SS, Madsen JK, Pedersen EB (1994) Systemic and renal effect of intravenous infusion of endothelin-1 in healthy human volunteers. Am J Physiol 266:F411–F418

    PubMed  CAS  Google Scholar 

  • Spieker LE, Corti R, Binggeli C, Lüscher TF, Noll G (2000a) Baroreceptor dysfunction induced by nitric oxide synthase inhibition in humans. J Am Coll Cardiol 36:213–218

    PubMed  CAS  Google Scholar 

  • Spieker LE, Noll G, Ruschitzka FT, Maier W, Lüscher TF (2000b) Working under pressure: the vascular endothelium in arterial hypertension. J Hum Hypertens 14:617–630

    PubMed  CAS  Google Scholar 

  • Spieker LE, Noll G, Ruschitzka FT, Lüscher TF (2001) Endothelin receptor antagonists in congestive heart failure: a new therapeutic principle for the future? J Am Coll Cardiol 37:1493–1505

    PubMed  CAS  Google Scholar 

  • Stamler JS, Singel DJ, Loscalzo J (1992) Biochemistry of nitric oxide and its redox-activated forms. Science 258:1898–1902

    PubMed  CAS  Google Scholar 

  • Stamler JS, Loh E, Roddy MA, Currie KE, Creager MA (1994) Nitric oxide regulates basal systemic and pulmonary vascular resistance in healthy humans. Circulation 89:2035–2040

    PubMed  CAS  Google Scholar 

  • Stevens PA, Brown MJ (1995) Genetic variability of the ET-1 and the ETA receptor genes in essential hypertension. J Cardiovasc Pharmacol 26Suppl 3:S9–S12

    PubMed  CAS  Google Scholar 

  • Stroes E, Hijmering M, van Zandvoort M, Wever R, Rabelink TJ, van Faassen EE (1998) Origin of superoxide production by endothelial nitric oxide synthase. FEBS Lett 438:161–164

    PubMed  CAS  Google Scholar 

  • Sudano I, Taddei S, Virdis A, Ghiadoni L, Haq BA, Noll G, Lüscher TF, Salvetti A (1998) Nifedipine enhances endothelium-dependent relaxation and inhibits contractions to endothelin-1 and phenylephrine in hypertension [abstract]. J Hypertens 16:1115

    Google Scholar 

  • Taddei S, Virdis A, Mattei P, Arzilli F, Salvetti A (1992) Endothelium-dependent forearm vasodilation is reduced in normotensive subjects with familial history of hypertension. J Cardiovasc Pharmacol 20:S193–S195

    PubMed  Google Scholar 

  • Taddei S, Mattei P, Virdis A, Sudano I, Ghiadoni L, Salvetti A (1994) Effect of potassium on vasodilation to acetylcholine in essential hypertension. Hypertension 23:485–490

    PubMed  CAS  Google Scholar 

  • Taddei S, Virdis A, Mattei P, Ghiadoni L, Gennari A, Fasolo CB, Sudano I, Salvetti A (1995) Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation 91:1981–1987

    PubMed  CAS  Google Scholar 

  • Taddei S, Virdis A, Mattei P, Ghiadoni L, Fasolo CB, Sudano I, Salvetti A (1997a) Hypertension causes premature aging of endothelial function in humans. Hypertension 29:736–743

    PubMed  CAS  Google Scholar 

  • Taddei S, Virdis A, Ghiadoni L, Magagna A, Salvetti A (1997b) Cyclooxygenase inhibition restores nitric oxide activity in essential hypertension. Hypertension 29:274–279

    PubMed  CAS  Google Scholar 

  • Taddei S, Virdis A, Ghiadoni L, Uleri S, Magagna A, Salvetti A (1997c) Lacidipine restores endothelium-dependent vasodilation in essential hypertensive patients. Hypertension 30:1606–1612

    PubMed  CAS  Google Scholar 

  • Taddei S, Virdis A, Ghiadoni L, Mattei P, Salvetti A (1998a) Effects of angiotensin converting enzyme inhibition on endothelium-dependent vasodilatation in essential hypertensive patients. J Hypertens 16:447–456

    PubMed  CAS  Google Scholar 

  • Taddei S, Virdis A, Ghiadoni L, Magagna A, Salvetti A (1998b) Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension. Circulation 97:2222–2229

    PubMed  CAS  Google Scholar 

  • Taddei S, Virdis A, Ghiadoni L, Sudano I, Notari M, Salvetti A (1999a) Vasoconstriction to endogenous endothelin-1 is increased in the peripheral circulation of patients with essential hypertension. Circulation 100:1680–1683

    PubMed  CAS  Google Scholar 

  • Taddei S, Ghiadoni L, Virdis A, Buralli S, Salvetti A (1999b) Vasodilation to bradykinin is mediated by an ouabain-sensitive pathway as a compensatory mechanism for impaired nitric oxide availability in essential hypertensive patients. Circulation 100:1400–1405

    PubMed  CAS  Google Scholar 

  • Takahashi M, Matsushita Y, Iijima Y, Tanzawa K (1993) Purification and characterization of endothelin-converting enzyme from rat lung. J Biol Chem 268:21394–21398

    PubMed  CAS  Google Scholar 

  • Takase B, Uehata A, Akima T, Nagai T, Nishioka T, Hamabe A, Satomura K, Ohsuzu F, Kurita A (1998) Endothelium-dependent flow-mediated vasodilation in coronary and brachial arteries in suspected coronary artery disease. Am J Cardiol 82:1535–9, A7–A8

    PubMed  CAS  Google Scholar 

  • Takase H, Moreau P, Kung CF, Nava E, Lüscher TF (1996) Antihypertensive therapy prevents endothelial dysfunction in chronic nitric oxide deficiency. Effect of verapamil and trandolapril. Hypertension 27:25–31

    PubMed  CAS  Google Scholar 

  • Tan DY, Meng S, Manning RD Jr (1999) Role of neuronal nitric oxide synthase in Dahl salt-sensitive hypertension. Hypertension 33:456–461

    PubMed  CAS  Google Scholar 

  • Taylor SG, Weston AH (1988) Endothelium-derived hyperpolarizing factor: a new endogenous inhibitor from the vascular endothelium. Trends Pharmacol Sci 9:272–274

    PubMed  CAS  Google Scholar 

  • Thomson L, Trujillo M, Telleri R, Radi R (1995) Kinetics of cytochrome c2+ oxidation by peroxynitrite: implications for superoxide measurements in nitric oxide-producing biological systems. Arch Biochem Biophys 319:491–497

    PubMed  CAS  Google Scholar 

  • Title LM, Giddens K, McInerney MM, McQueen MJ, Nassar BA (2003) Effect of cyclooxygenase-2 inhibition with rofecoxib on endothelial dysfunction and inflammatory markers in patients with coronary artery disease. J Am Coll Cardiol 42:1747–1753

    PubMed  CAS  Google Scholar 

  • Treasure CB, Klein JL, Vita JA, Manoukian SV, Renwick GH, Selwyn AP, Ganz P, Alexander RW (1993) Hypertension and left ventricular hypertrophy are associated with impaired endothelium-mediated relaxation in human coronary resistance vessels. Circulation 87:86–93

    PubMed  CAS  Google Scholar 

  • Tschudi MR, Criscione L, Novosel D, Pfeiffer K, Lüscher TF (1994) Antihypertensive therapy augments endothelium-dependent relaxations in coronary arteries of spontaneously hypertensive rats. Circulation 89:2212–2218

    PubMed  CAS  Google Scholar 

  • Tschudi MR, Mesaros S, Lüscher TF, Malinski T (1996) Direct in situ measurement of nitric oxide inmesenteric resistance arteries. Increased decomposition by superoxide in hypertension. Hypertension 27:32–35

    PubMed  CAS  Google Scholar 

  • Turrens JF, Boveris A (1980) Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. Biochem J 191:421–427

    PubMed  CAS  Google Scholar 

  • Vallance P, Collier J, Moncada S (1989) Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet 2:997–1000

    PubMed  CAS  Google Scholar 

  • van de Voorde J, Vanheel B, Leusen I (1992) Endothelium-dependent relaxation and hyperpolarization in aorta from control and renal hypertensive rats. Circ Res 70:1–8

    PubMed  Google Scholar 

  • van den Buuse M, Itoh S (1993) Central effects of endothelin on baroreflex of spontaneously hypertensive rats. J Hypertens 11:379–387

    PubMed  Google Scholar 

  • van Nueten L, De Cree J (1998) Nebivolol: comparison of the effects of dl-nebivolol, dnebivolol, l-nebivolol, atenolol, and placebo on exercise-induced increases in heart rate and systolic blood pressure. Cardiovasc Drugs Ther 12:339–344

    PubMed  Google Scholar 

  • Vandermeersch S, Stefanovic V, Hus-Citharel A, Ardaillou R, Dussaule JC, Chansel D (2003) AT1 receptor expression in glomeruli from NO-deficient rats. Nephron Exp Nephrol 95:e119–e128

    PubMed  CAS  Google Scholar 

  • Vanhoutte PM (1987) Vascular physiology: the end of the quest? [news]. Nature 327:459–460

    PubMed  CAS  Google Scholar 

  • Verma S, Raj SR, Shewchuk L, Mather KJ, Anderson TJ (2001) Cyclooxygenase-2 blockade does not impair endothelial vasodilator function in healthy volunteers: randomized evaluation of rofecoxib versus naproxen on endothelium-dependent vasodilatation. Circulation 104:2879–2882

    PubMed  CAS  Google Scholar 

  • Vierhapper H, Wagner O, Nowotny P, Waldhausl W (1990) Effect of endothelin-1 in man. Circulation 81:1415–1418

    PubMed  CAS  Google Scholar 

  • Wagner OF, Christ G, Wojta J, Vierhapper H, Parzer S, Nowotny PJ, Schneider B, Waldhausl W, Binder BR (1992) Polar secretion of endothelin-1 by cultured endothelial cells. J Biol Chem 267:16066–16068

    PubMed  CAS  Google Scholar 

  • Wallin BG, Sundlof G, Stromgren E, Aberg H (1984) Sympathetic outflow tomuscles during treatment of hypertension with metoprolol. Hypertension 6:557–562

    PubMed  CAS  Google Scholar 

  • Widlansky ME, Price DT, Gokce N, Eberhardt RT, Duffy SJ, Holbrook M, Maxwell C, Palmisano J, Keaney JF Jr, Morrow JD, Vita JA (2003) Short-and long-term COX-2 inhibition reverses endothelial dysfunction in patients with hypertension. Hypertension 42:310–315

    PubMed  CAS  Google Scholar 

  • Witte DR, Westerink J, de Koning EJ, van der Graaf Y, Grobbee DE, Bots ML (2005) Is the association between flow-mediated dilation and cardiovascular risk limited to low-risk populations? J Am Coll Cardiol 45:1987–1993

    PubMed  Google Scholar 

  • Woods M, Bishop-Bailey D, Pepper JR, Evans TW, Mitchell JA, Warner TD (1998) Cytokine and lipopolysaccharide stimulation of endothelin-1 release from human internal mammary artery and saphenous vein smooth-muscle cells. J Cardiovasc Pharmacol 31Suppl 1:S348–S350

    PubMed  CAS  Google Scholar 

  • Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T (1988) Anovel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411–415

    PubMed  CAS  Google Scholar 

  • Yang Z, Bauer E, von Segesser L, Stulz P, Turina M, Lüscher TF (1990a) Different mobilization of calcium in endothelin-1-induced contractions in human arteries and veins: effects of calcium antagonists. J Cardiovasc Pharmacol 16:654–660

    PubMed  CAS  Google Scholar 

  • Yang ZH, Richard V, von Segesser L, Bauer E, Stulz P, Turina M, Lüscher TF (1990b) Threshold concentrations of endothelin-1 potentiate contractions to norepinephrine and serotonin in human arteries. A new mechanism of vasospasm? Circulation 82:188–195

    PubMed  CAS  Google Scholar 

  • Yang ZH, von Segesser L, Bauer E, Stulz P, Turina M, Lüscher TF (1991) Different activation of the endothelial l-arginine and cyclooxygenase pathway in the human internal mammary artery and saphenous vein. Circ Res 68:52–60

    PubMed  CAS  Google Scholar 

  • Yang Z, Krasnici N, Lüscher TF (1999) Endothelin-1 potentiates smooth muscle cell growth to PDGF: role of ETA and ETB receptor blockade. Circulation 100:5–8

    PubMed  CAS  Google Scholar 

  • Yavuz D, Koc M, Toprak A, Akpinar I, Velioglu A, Deyneli O, Haklar G, Akalin S (2003) Effects of ACE inhibition and AT1-receptor antagonism on endothelial function and insulin sensitivity in essential hypertensive patients. J Renin Angiotensin Aldosterone Syst 4:197–203

    PubMed  CAS  Google Scholar 

  • Yoshizumi M, Kurihara H, Sugiyama T, Takaku F, Yanagisawa M, Masaki T, Yazaki Y (1989) Hemodynamic shear stress stimulates endothelin production by cultured endothelial cells. Biochem Biophys Res Commun 161:859–864

    PubMed  CAS  Google Scholar 

  • Zafari AM, Ushio-Fukai M, Akers M, Yin Q, Shah A, Harrison DG, Taylor WR, Griendling KK (1998) Role of NADH/NADPH oxidase-derived H2O2 in angiotensin II-induced vascular hypertrophy. Hypertension 32:488–495

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cardiovascular Centre, Cardiology, Dep. of Internal Medicine, University Hospital, 8091, Zürich, Switzerland

    L. E. Spieker, A. J. Flammer & T. F. Lüscher

  2. Institute of Physiology, Cardiovascular Research, University Zürich Irchel, 8057, Zürich, Switzerland

    L. E. Spieker, A. J. Flammer & T. F. Lüscher

Authors
  1. L. E. Spieker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. J. Flammer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. F. Lüscher
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. The Wolfson Institute for Biomedical Research, University College London, Gower Street, London, WC1E 6BT, UK

    Salvador Moncada FRCP FRS  & Annie Higgs  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Spieker, L.E., Flammer, A.J., Lüscher, T.F. (2006). The Vascular Endothelium in Hypertension. In: Moncada, S., Higgs, A. (eds) The Vascular Endothelium II. Handbook of Experimental Pharmacology, vol 176/II. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-36028-X_8

Download citation

Publish with us

Policies and ethics

Search

Navigation