Adenosine-mediated early preconditioning in mouse: protective signaling and concentration dependent effects

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Title Adenosine-mediated early preconditioning in mouse: protective signaling and concentration dependent effects
Author Peart, Jason Nigel John; Headrick, John Patrick
Journal Name Cardiovascular Research
Year Published 2003
Place of publication Netherlands
Publisher Elsevier BV
Abstract Objective: α1-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 α1-AR subtypes (α1A, α1B and α1D) to cardiac function is not clearly defined. In this study, we used a systemically expressing mouse model that overexpresses the α1B-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 α1B-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 α1A-AR antagonist, 5-methylurapidil, which correlated with decreases in α1A-AR density, suggesting that the α1B-AR had caused a compensatory downregulation of the α1A-AR. Conclusions: These results suggest that the α1B-AR does not have a major role in the positive inotropic response in the mouse myocardium but may negatively modulate the response of the α1A-AR.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1016/S0008-6363(03)00259-1
Volume 58
Page from 589
Page to 601
ISSN 0008-6363
Date Accessioned 2004-04-07
Date Available 2015-05-04T22:03:49Z
Language en_US
Research Centre Menzies Health Institute Qld; Heart Foundation Research Centre
Faculty Griffith Health Faculty
Subject PRE2009-Medical Physiology
URI http://hdl.handle.net/10072/6139
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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