CB1 cannabinoid receptor antagonism promotes remodeling and cannabinoid treatment prevents endothelial dysfunction and hypotension in rats with myocardial infarction

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Abstract
To study the long‐term effects of altered cannabinoid receptor activity on myocardial and vascular function, Wistar rats were treated with the selective CB1 antagonist AM‐251 (0.5 mg kg−1 d−1), the potent synthetic cannabinoid HU‐210 (50 μg kg−1 d−1) or vehicle for 12 weeks after coronary artery ligation or sham operation. AM‐251 further reduced the pressure‐generating capacity, shifted the pressure volume curve to the right (Pμl vs control: 820±40 μl vs HU‐210: 790±50 μl; P1 immunoactivity in rats 12 weeks after large MI was unaltered as compared with noninfarcted hearts. Cannabinoid receptor activation through HU‐210, a cannabinoid that alters cardiovascular parameters via CB1 receptors, increased the left‐ventricular end‐diastolic pressure (LVEDP, PPvs control: 124±3 mm Hg; and Pvs AM‐251: 114±3 mm Hg) and prevented endothelial dysfunction (ED) in aortic rings of rats with large MI (PPPP1 antagonism promotes remodeling despite unchanged myocardial CB1 expression. British Journal of Pharmacology (2003) 138, 1251–1258. doi:10.1038/sj.bjp.0705156