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Endogenous cannabinoids mediate hypotension after experimental myocardial infarction
Journal of the American College of Cardiology, Volume 38, Issue 7, December 2001, Pages 2048-2054
Jens A. Wagner MD, Kai Hu MD, Johann Bauersachs MD, Jan Karcher, Martina Wiesler ...

Abstract: ObjectivesWe sought to determine whether endocannabinoids influence hemodynamic variables in experimental models of acute myocardial infarction (MI).BackgroundHypotension and cardiogenic shock are common complications in acute MI. Cannabinoids are strong vasodilators, and endocannabinoids are involved in hypotension in hemorrhagic and septic shock.MethodsThe early effect of left coronary artery ligation on hemodynamic variables was measured in rats pretreated with the selective cannabinoid1 receptor (CB1) antagonist SR141716A (herein referred to as SR, 6.45 μmol/kg body weight intravenously) or vehicle. Endocannabinoids produced in monocytes and platelets were quantified by liquid chromatography/mass spectrometry (LC/MS), and their effects on blood pressure and vascular reactivity were determined.ResultsAfter MI, mean arterial pressure (MAP) dropped from 126 ± 2 mm Hg to 76 ± 3 mm Hg in control rats, whereas the decline in blood pressure was smaller (from 121 ± 3 mm Hg to 108 ± 7 mm Hg, p < 0.01) in rats pretreated with SR. SR increased the tachycardia that follows MI (change [Δ] in heart rate [HR] = 107 ± 21 beats/min vs. 49 ± 9 beats/min in control rats, p < 0.05). The MI sizes were the same in control rats and SR-treated rats. Circulating monocytes and platelets isolated 30 min after MI only decreased MAP when injected into untreated rats (ΔMAP = −20 ± 5 mm Hg), but not in SR-pretreated rats. The endocannabinoids anandamide and 2-arachidonyl glycerol were detected in monocytes and platelets isolated after MI, but not in cells from sham rats. Survival rates at 2 h after MI were 70% for control rats and 36% for SR-treated rats (p < 0.05). Endothelium-dependent arterial relaxation was attenuated in SR-treated rats (maximal relaxation: 44 ± 3% [p < 0.01] vs. 70 ± 3% in control rats) and further depressed by SR treatment (24 ± 5%, p < 0.01 vs. MI placebo).ConclusionsCannabinoids generated in monocytes and platelets contribute to hypotension in acute MI. Cannabinoid1 receptor blockade restores MAP but increases 2-h mortality, possibly by impairing endothelial function.

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