Contractile effects of angiotensin and endothelin in failing and non-failing human hearts

International Journal of Cardiology
Helge MöllmannChristian J F Holubarsch

Abstract

Angiotensin II (Ang II) and endothelin-1 (ET-1) share their effects on growth of myocardial cells but have been shown to elicit different effects on myocardial function. However, these effects vary markedly among species, cardiac regions (atrium or ventricle) and failing or non-failing myocardium. We therefore investigated the effects of both peptides on contractile function of isolated human myocytes from failing and non-failing hearts. Cardiomyocytes were enzymatically isolated and electrically stimulated (15 V, 0.2 Hz). Ang II elicited a positive inotropic effect (PIE) mediated by activation of protein kinase C (PKC) in atrial but no effect in ventricular myocytes. ET-1 (10(-8) M) increased cell-shortening by 146+/-9.3% (p<0.05) in atrial myocytes, by 99.1+/-16.5% (p<0.05) in non-failing ventricular but only by 40.5+/-6.4% (p<0.05) in failing ventricular myocytes. The PIE of ET-1 in failing myocytes was more pronounced at low extracellular pH (+112.6+/-27% at pH 7.0 vs. +40.5+/-6.4% at pH 7.4, p<0.05). Amiloride, a sodium-hydrogen-exchange inhibitor, inhibited two thirds of the PIE of ET-1 in failing myocytes. The PKC-inhibitor decreased the PIE by 50% from 113% to 64% in ventricular myocytes under acidotic conditions. Ang I...Continue Reading

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Citations

Mar 5, 2015·International Journal of Molecular Medicine·Huixin GuoYidong Wei
Jul 7, 2011·Scandinavian Journal of Clinical and Laboratory Investigation·Kristine B OlsenMorten S Nielsen
Jul 26, 2008·The Journal of International Medical Research·H MöllmannA Elsässer
Sep 23, 2008·Journal of Hypertension·Pietro Amedeo ModestiAlessandra Modesti
Jun 15, 2007·Physiology·Misuk KangJeffery W Walker
Mar 11, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Ka Young ChungJeffery W Walker
Jan 25, 2020·Molecular Medicine Reports·Huijun ChengYoujun Zhou

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