Cannabinoids acting on CB1 receptors decrease contractile performance in human atrial muscle
- PMID: 12658069
- DOI: 10.1097/00005344-200304000-00020
Cannabinoids acting on CB1 receptors decrease contractile performance in human atrial muscle
Abstract
Cannabinoids elicit hypotension mainly via activated CB(1) receptors and show complex cardiovascular actions. Effects on human heart muscle have not been studied yet. Isolated human atrial heart muscle preparations were stimulated by electrical field with 1 Hz to contract isometrically at optimal length and were challenged with the endogenous cannabinoid arachidonyl ethanolamide (anandamide), the metabolically stable analogue R-methanandamide, and the potent synthetic CB(1) receptor agonist HU-210. Anandamide dose-dependently decreased systolic force (82.2 +/- 4.8% and 60.8 +/- 6.8% of maximal systolic force for 0.1 and 1 microM, respectively, P < 0.05). The selective CB(1) receptor antagonist AM-251 (1 microM, P < 0.05), but not the CB(2) receptor antagonist, AM-630 (1 microM), the nitric oxide synthase inhibitor N omega-nitro-l-arginine methyl ester (l-NAME) (500 microM), or the cyclooxygenase inhibitor indomethacin (100 microM), prevented the effect. Contrary to indomethacin, l-NAME alone showed negative inotropic effects (72.1 +/- 3.54%, P < 0.001). The R-methanandamide (1 microM: 50.4 +/- 3.5%, P < 0.001) and HU-210 (1 microM: 60.1 +/- 3.8%, P < 0.001) had similar negative inotropic effects. The existence of CB(1) receptors on heart muscle was verified using Western blot analysis and immunofluorescence staining. The conclusion is that anandamide, R-methanandamide, and HU-210 decrease contractile performance in human atrial muscle via CB(1) receptors.
Similar articles
-
Hemodynamic effects of cannabinoids: coronary and cerebral vasodilation mediated by cannabinoid CB(1) receptors.Eur J Pharmacol. 2001 Jul 6;423(2-3):203-10. doi: 10.1016/s0014-2999(01)01112-8. Eur J Pharmacol. 2001. PMID: 11448486
-
Contractile response to a cannabimimetic eicosanoid, 2-arachidonoylglycerol, of longitudinal smooth muscle from the guinea-pig distal colon in vitro.Eur J Pharmacol. 2002 May 31;444(3):203-7. doi: 10.1016/s0014-2999(02)01650-3. Eur J Pharmacol. 2002. PMID: 12063081
-
Cannabinoid CB(1) receptor activation modulates spontaneous contractile activity in mouse ileal longitudinal muscle.Eur J Pharmacol. 2008 Mar 17;582(1-3):132-8. doi: 10.1016/j.ejphar.2007.12.016. Epub 2007 Dec 27. Eur J Pharmacol. 2008. PMID: 18234188
-
Cardiovascular actions of cannabinoids and their generation during shock.J Mol Med (Berl). 1998 Nov-Dec;76(12):824-36. doi: 10.1007/s001090050287. J Mol Med (Berl). 1998. PMID: 9846953 Review.
-
Cannabinoid receptors and their ligands.Prostaglandins Leukot Essent Fatty Acids. 2002 Feb-Mar;66(2-3):101-21. doi: 10.1054/plef.2001.0341. Prostaglandins Leukot Essent Fatty Acids. 2002. PMID: 12052030 Review.
Cited by
-
Cannabinoid antagonist SR-141716 inhibits endotoxic hypotension by a cardiac mechanism not involving CB1 or CB2 receptors.Am J Physiol Heart Circ Physiol. 2004 Aug;287(2):H595-600. doi: 10.1152/ajpheart.00184.2004. Epub 2004 Apr 1. Am J Physiol Heart Circ Physiol. 2004. PMID: 15059774 Free PMC article.
-
Cannabinoid Receptor 1 Inhibition in Chronic Kidney Disease: A New Therapeutic Toolbox.Front Endocrinol (Lausanne). 2021 Jul 7;12:720734. doi: 10.3389/fendo.2021.720734. eCollection 2021. Front Endocrinol (Lausanne). 2021. PMID: 34305821 Free PMC article. Review.
-
Anandamide reduces intracellular Ca2+ concentration through suppression of Na+/Ca2+ exchanger current in rat cardiac myocytes.PLoS One. 2013 May 7;8(5):e63386. doi: 10.1371/journal.pone.0063386. Print 2013. PLoS One. 2013. PMID: 23667607 Free PMC article.
-
Cardiovascular pharmacology of cannabinoids.Handb Exp Pharmacol. 2005;(168):599-625. doi: 10.1007/3-540-26573-2_20. Handb Exp Pharmacol. 2005. PMID: 16596789 Free PMC article. Review.
-
Role of Cannabinoid Signaling in Cardiovascular Function and Ischemic Injury.J Pharmacol Exp Ther. 2023 Dec;387(3):265-276. doi: 10.1124/jpet.123.001665. Epub 2023 Sep 22. J Pharmacol Exp Ther. 2023. PMID: 37739804 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous