Journal
CARDIOVASCULAR RESEARCH
Volume 60, Issue 3, Pages 598-607Publisher
OXFORD UNIV PRESS
DOI: 10.1016/j.cardiores.2003.09.020
Keywords
adrenergic receptor; heart; myocyte; inotropy
Categories
Funding
- NHLBI NIH HHS [R01HL31820-11, T32HL07914, R01HL614380-04] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [T32HL007914] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Objective: alpha(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 alpha(1)-AR subtypes (alpha(1A), alpha(1B) and alpha(1D)) to cardiac function is not clearly defined. In this study, we used a systemically expressing mouse model that overexpresses the alpha(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 alpha(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 alpha(1A)-AR antagonist, 5-methylurapidil, which correlated with decreases in alpha(1A)-AR density, suggesting that the alpha(1B)-AR had caused a compensatory downregulation of the alpha(1A)-AR. Conclusions: These results suggest that the alpha(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 alpha(1A)-AR. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available