Endogenous cannabinoids mediate hypotension after experimental myocardial infarction

OBJECTIVES We sought to determine whether endocannabinoids influence hemody namic variables in an experimental models of acute myocardial infarction (M I). BACKGROUND Hypotension and cardiogenic shock are common complications in ac ute MI. Cannabinoids are strong vasodilators, and endocannabinoids are invo lved in hypotension in hemorrhagic and septic shock. METHODS The early effect of left coronary artery ligation on hemodynamic va riables was measured in rats pretreated with the selective cannabinoid, rec eptor (CB1) antagonist SR141716A (herein referred to as SR, 6.45 mu mol/kg body weight intravenously) or vehicle. Endocannabinoids produced in monocyt es and platelets were quantified by liquid chromatography/mass spectrometry (LC/MS), and their effects on blood pressure and vascular reactivity were determined. RESULTS After MI, mean arterial pressure (MAP) dropped from 126 +/- 2 min H g to 76 +/- 3 mm Hg in control rats, whereas the decline in blood pressure was smaller (from 121 3 mm Hg to 108 +/- 7 min Hg, p < 0.01) in rats pretre ated with SR. SR increased the tachycardia that follows MI (change [<Delta> ] in heart rate [HR] = +107 +/- 21 beate/min vs. + 49 +/- 9 beats/min in co ntrol rats, p < 0.05). The MI sizes were the same in control rats and SR-tr eated rats. Circulating monocytes and platelets isolated 30 min after MI on ly, decreased MAP when injected into untreated rats (<Delta>MAP = -20 +/- 5 min Hg), but not in SR-pretreated rats. The endocannabinoids anandamide an d 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 w ere 70% for control rats and 36% for SR-treated rats (p < 0.05). Endotheliu m-dependent arterial relaxation was attenuated after MI (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). CONCLUSIONS Cannabinoids generated in monocytes and platelets contribute to hypotension in acute MI. Cannabinoid, receptor blockade restores MAP but i ncreases 2-h mortality, possibly by impairing endothelial function. (J Am C oll Cardiol 2001;38:2048-54) (C) 2001 by the American College of Cardiology .