Upregulation of β 3 -Adrenoceptors and Altered Contractile Response to Inotropic Amines in Human Failing Myocardium
- 27 March 2001
- journal article
- other
- Published by Wolters Kluwer Health in Circulation
- Vol. 103 (12) , 1649-1655
- https://doi.org/10.1161/01.cir.103.12.1649
Abstract
Background—Contrary to β1- and β2-adrenoceptors, β3-adrenoceptors mediate a negative inotropic effect in human ventricular muscle. To assess their functional role in heart failure, our purpose was to compare the expression and contractile effect of β3-adrenoceptors in nonfailing and failing human hearts. Methods and Results—We analyzed left ventricular samples from 29 failing (16 ischemic and 13 dilated cardiomyopathic) hearts (ejection fraction 18.6±2%) and 25 nonfailing (including 12 innervated) explanted hearts (ejection fraction 64.2±3%). β3-Adrenoceptor proteins were identified by immunohistochemistry in ventricular cardiomyocytes from nonfailing and failing hearts. Contrary to β1-adrenoceptor mRNA, Western blot analysis of β3-adrenoceptor proteins showed a 2- to 3-fold increase in failing compared with nonfailing hearts. A similar increase was observed for Gαi-2 proteins that couple β3-adrenoceptors to their negative inotropic effect. Contractile tension was measured in electrically stimulated myoca...Keywords
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