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

摘要: 1. To study the long-term effects of altered cannabinoid receptor activity on myocardial and vascular function, Wistar rats were treated with selective CB(1) antagonist AM-251 (0.5 mg kg(-1) d(-1)), potent synthetic HU-210 (50 micro g d(-1)) or vehicle for 12 weeks after coronary artery ligation sham operation. 2. further reduced pressure-generating capacity, shifted pressure volume curve to right (P<0.05) increased left-ventricular operating (AM-251: 930+/-40 l vs control: 820+/-40 HU-210: 790+/-50 l; P<0.05) in large infarction (MI). 3. Left-ventricular immunoactivity MI was unaltered as compared noninfarcted hearts. 4. Cannabinoid activation through HU-210, a that alters cardiovascular parameters via receptors, end-diastolic (LVEDP, P<0.05). However, it prevented drop systolic (HU-210: 142+/-5 mm Hg; P<0.05 124+/-3 P<0.001 AM-251: 114+/-3 Hg) endothelial dysfunction (ED) aortic rings (P<0.05). 5. Compared AM-251, decline maximal rate rise maximum ability In small MI, cardiac index (P<0.01) lowered total peripheral resistance 6. The shows during development congestive heart failure post-large treatment increases LVEDP prevents hypotension ED. Presumed antagonism promotes remodeling despite unchanged expression.