CB(1) cannabinoid receptor antagonism promotes remodeling and cannabinoid treatment prevents endothelial dysfunction and hypotension in rats with myocardial infarction.
Br J Pharmacol
; 138(7): 1251-8, 2003 Apr.
Article
in En
| MEDLINE
| ID: mdl-12711625
ABSTRACT
1. To study the long-term effects of altered cannabinoid receptor activity on myocardial and vascular function, Wistar rats were treated with the selective CB(1) antagonist AM-251 (0.5 mg kg(-1) d(-1)), the potent synthetic cannabinoid HU-210 (50 micro g kg(-1) d(-1)) or vehicle for 12 weeks after coronary artery ligation or sham operation. 2. AM-251 further reduced the pressure-generating capacity, shifted the pressure volume curve to the right (P<0.05) and increased the left-ventricular operating volume (AM-251 930+/-40 micro l vs control 820+/-40 micro l vs HU-210 790+/-50 micro l; P<0.05) in rats with large myocardial infarction (MI). 3. Left-ventricular CB(1) immunoactivity in rats 12 weeks after large MI was unaltered as compared with noninfarcted hearts. 4. Cannabinoid receptor activation through HU-210, a cannabinoid that alters cardiovascular parameters via CB(1) receptors, increased the left-ventricular end-diastolic pressure (LVEDP, P<0.05). However, it prevented the drop in left-ventricular systolic pressure (HU-210 142+/-5 mm Hg; P<0.05 vs control 124+/-3 mm Hg; and P<0.001 vs AM-251 114+/-3 mm Hg) and prevented endothelial dysfunction (ED) in aortic rings of rats with large MI (P<0.05). 5. Compared with AM-251, HU-210 prevented the decline in the maximal rate of rise of left-ventricular pressure and the maximum pressure-generating ability (P<0.05). In rats with small MI, HU-210 increased cardiac index (P<0.01) and lowered the total peripheral resistance (P<0.05). 6. The study shows that during the development of congestive heart failure post-large MI, cannabinoid treatment increases LVEDP and prevents hypotension and ED. Presumed CB(1) antagonism promotes remodeling despite unchanged myocardial CB(1) expression.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cannabinoids
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Hypertrophy, Left Ventricular
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Ventricular Remodeling
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Receptors, Cannabinoid
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Endothelium
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Cannabinoid Receptor Antagonists
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Hypotension
Limits:
Animals
Language:
En
Journal:
Br J Pharmacol
Year:
2003
Document type:
Article
Affiliation country: