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: ±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.
Peer Reviewed Yes
Published Yes
Publisher URI http://www.elsevier.com/wps/find/journaldescription.cws_home/525398/description#description
Copyright Statement Copyright 2003 Elsevier : Reproduced in accordance with the copyright policy of the publisher : This journal is available online - use hypertext links.
Volume 58
Page from 589
Page to 601
ISSN 0008-6363
Date Accessioned 2004-04-07
Language en_AU
Research Centre Heart Foundation Research Centre; Griffith Health Institute
Faculty Griffith Health Faculty
Subject Medical Physiology
URI http://hdl.handle.net/10072/6139
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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