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Effects of different beta adrenoceptor ligands in mice with permanent occlusion of the left anterior descending coronary artery
Author(s) -
CallaertsVegh Zsuzsanna,
Evans Kenda L J,
Shipley Gregory L,
Davies Peter J A,
Cuba Donald L,
Gurji Hunaid A,
Giles Heather,
Bond Richard A
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705205
Subject(s) - carvedilol , isoprenaline , in vivo , medicine , cardiology , vasodilation , artery , atenolol , isometric exercise , occlusion , pharmacology , endocrinology , biology , heart failure , blood pressure , microbiology and biotechnology , stimulation
We have studied the effects of three β AR ligands (carvedilol, alprenolol, and ICI‐118,551) with different pharmacological profiles and negative efficacy at the β 2AR on cardiac in vivo , in vitro , biochemical and gene expression parameters in mice with permanent occlusion of the left anterior descending coronary artery. Cardiac in vivo parameters were determined using Doppler studies. Mitral‐wave E peak velocity (EPV) and aortic peak velocity (AoPV) decreased in the first 2 weeks postocclusion. After 3 weeks of drug treatment, EPV was improved in the carvedilol group to preocclusion values; however, a further reduction in EPV in the alprenolol and control permanent occlusion group was measured and there was no change after ICI‐118,551 treatment. AoPV was unchanged between weeks 2 and 5 in all groups. The left atria were isolated to record isometric tension responses to isoprenaline. Permanent occlusion significantly reduced the maximum isoprenaline response to 30% of control and carvedilol increased the maximum response to isoprenaline significantly to 60%. The biochemical and gene expression studies revealed different effects of the three β AR ligands. Most notably, carvedilol reduced gene expression of myosin heavy chain β . These results indicate that chronic treatment with carvedilol is beneficial in a mouse model of myocardial damage resulting from ischaemia. We hypothesise that these beneficial effects of the drug may be because of the negative efficacy at the β 2AR, combined with β 1AR antagonism.British Journal of Pharmacology (2003) 138 , 1505–1516. doi: 10.1038/sj.bjp.0705205