Author + information
- Received April 24, 2001
- Revision received August 15, 2001
- Accepted August 29, 2001
- Published online December 1, 2001.
- Jens A Wagner, MDa,* (, )
- Kai Hu, MDa,
- Johann Bauersachs, MDa,
- Jan Karchera,
- Martina Wieslera,
- Sravan K Goparaju, PhDb,
- George Kunos, MD, PhDb and
- Georg Ertl, MDa
- ↵*Reprint requests and correspondence:
Dr. Jens A. Wagner, Department of Medicine, University of Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany.
Objectives We sought to determine whether endocannabinoids influence hemodynamic variables in experimental models of acute myocardial infarction (MI).
Background Hypotension and cardiogenic shock are common complications in acute MI. Cannabinoids are strong vasodilators, and endocannabinoids are involved in hypotension in hemorrhagic and septic shock.
Methods The early effect of left coronary artery ligation on hemodynamic variables was measured in rats pretreated with the selective cannabinoid1receptor (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.
Results After 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).
Conclusions Cannabinoids generated in monocytes and platelets contribute to hypotension in acute MI. Cannabinoid1receptor blockade restores MAP but increases 2-h mortality, possibly by impairing endothelial function.
- Received April 24, 2001.
- Revision received August 15, 2001.
- Accepted August 29, 2001.
- American College of Cardiology