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Title: Effects of different beta adrenoceptor ligands in mice with permanent occlusion of the left anterior descending coronary artery
Authors: Callaerts-Vegh, Zsuzsanna ×
Evans, Kenda L J
Shipley, Gregory L
Davies, Peter J A
Cuba, Donald L
Gurji, Hunaid A
Giles, Heather
Bond, Richard A #
Issue Date: Apr-2003
Publisher: Scientific & Medical Division, Macmillan Press
Series Title: British Journal of Pharmacology vol:138 issue:8 pages:1505-1516
Abstract: 1. We have studied the effects of three betaAR ligands (carvedilol, alprenolol, and ICI-118551) with different pharmacological profiles and negative efficacy at the beta2AR on cardiac in vivo, in vitro, biochemical and gene expression parameters in mice with permanent occlusion of the left anterior descending coronary artery. 2. 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-118551 treatment. AoPV was unchanged between weeks 2 and 5 in all groups. 3. 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%. 4. The biochemical and gene expression studies revealed different effects of the three betaAR ligands. Most notably, carvedilol reduced gene expression of myosin heavy chain beta. 5. 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 beta2AR, combined with beta1AR antagonism.
ISSN: 0007-1188
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Biological Psychology
Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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