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. 2007 Nov;293(5):H2971-6.
doi: 10.1152/ajpheart.00219.2007. Epub 2007 Aug 31.

Reactive oxygen species contribute to sleep apnea-induced hypertension in rats

Carmen M Troncoso Brindeiro  1 , Ana Q da Silva, Kyan J Allahdadi, Victoria Youngblood, Nancy L Kanagy
Affiliations

Reactive oxygen species contribute to sleep apnea-induced hypertension in rats

Carmen M Troncoso Brindeiro et al. Am J Physiol Heart Circ Physiol. 2007 Nov.

Abstract

In clinical studies, sleep apnea is associated with hypertension, oxidative stress, and increased circulating endothelin-1 (ET-1). We previously developed a model of sleep apnea by exposing rats to eucapnic intermittent hypoxia (IH-C) during sleep, which increases both blood pressure and plasma levels of ET-1. Because similar protocols in mice increase tissue and plasma markers of oxidative stress, we hypothesized that IH-C generation of reactive oxygen species (ROS) contributes to the development of ET-1-dependent hypertension in IH-C rats. To test this, male Sprague-Dawley rats were instrumented with indwelling blood pressure telemeters and drank either plain water or water containing the superoxide dismutase mimetic, Tempol (4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl, 1 mM). Mean arterial pressure (MAP) and heart rate (HR) were recorded for 3 control days and 14 treatment days with rats exposed 7 h/day to IH-C or air/air cycling (Sham). On day 14, MAP in IH-C rats treated with Tempol (107 +/- 2.29 mmHg) was significantly lower than in untreated IH-C rats (118 +/- 9 mmHg, P < 0.05). Tempol did not affect blood pressure in sham-operated rats (Tempol = 101 +/- 3, water = 101 +/- 2 mmHg). Immunoreactive ET-1 was greater in plasma from IH-C rats compared with plasma from sham-operated rats but was not different from Sham in Tempol-treated IH-C rats. Small mesenteric arteries from IH-C rats but not Tempol-treated IH-C rats had increased superoxide levels as measured by ferric cytochrome c reduction, lucigenin signaling, and dihydroethidium fluorescence. The data show that IH-C increases ET-1 production and vascular ROS levels and that scavenging superoxide prevents both. Thus oxidative stress appears to contribute to increases in ET-1 production and elevated arterial pressure in this rat model of sleep apnea-induced hypertension.

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Figures

Fig. 1
Fig. 1
Mean arterial blood pressure (MAP) was recorded daily for 3 baseline days and 14 treatment days in eucapnic intermittent hypoxia (IH-C) ±Tempol and Sham ± Tempol (T). MAP increased in IH-C-vehicle rats over the 14 days of treatment. MAP did not increase in IH-C rats treated with Tempol (1 mM). Tempol did not affect MAP in sham-operated rats. *P < 0.05, significant difference from Sham/vehicle.
Fig. 2
Fig. 2
Tiron-sensitive O2- generation measured as change in absorbance at 550 nm (A550) of a ferric cytochrome c solution was greater in mesenteric arteries from 14-day IH-C rats (A) than in arteries from 14-day Sham rats but not in arteries from IH-C rats treated with Tempol (B) compared with arteries from Sham rats treated with Tempol. Data presented are vehicle (Veh) A550–tiron-insensitive A550.
Fig. 3
Fig. 3
Basal and NADPH-stimulated lucigenin luminescence was greater in mesenteric arteries from IH-C rats (n = 8) than in arteries from Sham rats (n = 10). *P < 0.05, significant difference from Sham.
Fig. 4
Fig. 4
Dihydroethidium fluorescence was greater in IH-C arteries than in Sham arteries. Tempol treatment in vivo prevented the IH-C-stimulated increase but did not affect the signal in arteries from Sham rats. *Significant difference from Sham; #Significant difference from vehicle within group.
Fig. 5
Fig. 5
Plasma concentration of endothelin (ET-1) in blood samples taken from rats exposed to 14 days of either Sham or IH-C cycling and drinking either tap water or water containing Tempol (1 mmol/l). [ET-1] was significantly greater in plasma from IH-C rats compared with plasma from sham-operated rats and plasma from Tempol-treated IH-C rats (P < 0.05). *Significant difference from Sham; #Significant difference from vehicle within group.
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References

    1. Baguet JP, Narkiewicz K, Mallion JM. Update on Hypertension Management: obstructive sleep apnea and hypertension. J Hypertens. 2006;24:205–208. - PubMed
    1. Bao G, Randhawa PM, Fletcher EC. Acute blood pressure elevation during repetitive hypocapnic and eucapnic hypoxia in rats. J Appl Physiol. 1997;82:1071–1078. - PubMed
    1. Boland LL, Shahar E, Iber C, Knopman DS, Kuo TF, Nieto FJ. Measures of cognitive function in persons with varying degrees of sleep-disordered breathing: the Sleep Heart Health Study. J Sleep Res. 2002;11:265–272. - PubMed
    1. Cheng TH, Cheng PY, Shih NL, Chen IB, Wang DL, Chen JJ. Involvement of reactive oxygen species in angiotensin II-induced endothelin-1 gene expression in rat cardiac fibroblasts. J Am Coll Cardiol. 2003;42:1845–1854. - PubMed
    1. Cheng TH, Shih NL, Chen SY, Loh SH, Cheng PY, Tsai CS, Liu SH, Wang DL, Chen JJ. Reactive oxygen species mediate cyclic strain-induced endothelin-1 gene expression via Ras/Raf/extracellular signal-regulated kinase pathway in endothelial cells. J Mol Cell Cardiol. 2001;33:1805–1814. - PubMed

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