© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
The 
1B-adrenergic receptor decreases the inotropic response in the mouse Langendorff heart model
aThe Department of Molecular Cardiology NB50, The Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA
bThe Department of Pharmacology and the Vascular Biology Research Group, The University of Kentucky College of Medicine, Lexington, KY 40536, USA
*Corresponding author. Tel.: +1-216-444-2058; fax: +1-216-444-9263. Email address: perezd{at}ccf.org
Objective: 
1-Adrenergic receptors (ARs) are known mediators of a positive inotropy in the heart, which may play even more important roles in heart disease. Due to a lack of sufficiently selective ligands, the contribution of each of the three 1-AR subtypes (1A, 1B and 1D) to cardiac function is not clearly defined. In this study, we used a systemically expressing mouse model that overexpresses the 1B-AR to define the role of this subtype in cardiac function. Methods: We used the mouse Langendorff heart model to assess changes in contractility under basal and phenylephrine-induced conditions. Results: We find that a 50% increase of the 1B-AR in the heart does not change basal cardiac parameters compared to age-matched normals (heart rate, ±dP/dT and coronary flow). However, the inotropic response to phenylephrine is blunted. The same results were obtained in isolated adult myocytes. The difference in inotropy could be blocked by the selective 1A-AR antagonist, 5-methylurapidil, which correlated with decreases in 1A-AR density, suggesting that the 1B-AR had caused a compensatory downregulation of the 1A-AR. Conclusions: These results suggest that the 1B-AR does not have a major role in the positive inotropic response in the mouse myocardium but may negatively modulate the response of the 1A-AR.
KEYWORDS Adrenergic receptor; Heart; Myocyte; Inotropy
1 Present Address: GlaxoSmithKline, Research Triangle Park, NC.
Time for primary review 48 days
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