Chronic ventricular myocyte-specific overexpression of angiotensin II type 2 receptor results in intrinsic myocyte contractile dysfunction

American Journal of Physiology. Heart and Circulatory Physiology
Masaharu NakayamaB H Lorell

Abstract

ANG II type 2 receptor (AT(2)) is upregulated in failing hearts, but its effect on myocyte contractile function is not known. We measured fractional cell shortening and intracellular Ca(2+) concentration transients in left ventricular myocytes derived from transgenic mice in which ventricle-specific expression of AT(2) was driven by the myosin light chain 2v promoter. Confocal microscopy studies confirmed upregulation of AT(2) in the ventricular myocytes and partial colocalization of AT(2) with AT(1). Three components of contractile performance were studied. First, baseline measurements (0.5 Hz, 1.5 mmol/l extracellular Ca(2+) concentration, 25 degrees C) and study of contractile reserve at faster pacing rates (1-5 Hz) revealed Ca(2+)-dependent contractile dysfunction in myocytes from AT(2) transgenic mice. Comparison of two transgenic lines suggested a dose-dependent relationship between magnitude of contractile dysfunction and level of AT(2) expression. Second, activity of the Na(+)/H(+) exchanger, a dominant transporter that regulates beat-to-beat intracellular pH, was impaired in the transgenic myocytes. Third, the inotropic response to beta-adrenergic versus ANG II stimulation differed. Both lines showed impaired contracti...Continue Reading

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Citations

Jan 8, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Xinhua YanJames P Morgan
Nov 24, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Sam E SawayaDirar S Khoury
Jul 1, 2016·Clinical Science·Bryna S M Chow, Terri J Allen
Dec 14, 2019·American Journal of Physiology. Heart and Circulatory Physiology·Paula D Mullins, Vladimir E Bondarenko
Sep 2, 2017·Scientific Reports·Tamara HermosillaDiego Varela
Sep 16, 2017·Frontiers in Pharmacology·Yan WangRobert E Widdop
Jul 30, 2020·PloS One·Natia Q KelmSham S Kakar
Apr 12, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yuanji MaJunbo Ge

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