Exogenous effects and endogenous production of endothelin in cardiac myocytes: potential significance in heart failure

The American Journal of Physiology
P B ThomasF G Spinale

Abstract

Increased plasma concentrations of endothelin have been identified in patients and animals with severe congestive heart failure (CHF). However, whether and to what extent increased endothelin (ET) concentrations influence left ventricular (LV) myocyte contractility, ET-receptor subtype density, and endogenous ET production with the development of CHF remains unclear. Accordingly, myocyte contractile function, response to ET, sarcolemmal ET-receptor density, and myocyte ET production were examined in pigs following the development of pacing-induced CHF (240 beats/min, 3 wk, n = 8) and in controls (n = 8). With CHF, plasma ET increased over threefold. In the presence of ET (10-500 pM), myocyte contractility increased in a dose-dependent manner in control myocytes but decreased in CHF myocytes. For example, in the presence of 200 pM ET, velocity of shortening increased by 32.8 +/- 2.3 microns/s in controls but decreased by 8.3 +/- 2.2 microns/s with CHF. LV sarcolemmal ET-receptor density was primarily of the ETA-receptor subtype in controls (96 +/- 1.0%) and was unchanged with CHF. In quiescent myocyte preparations, control myocytes secreted ET (2.29 +/- 0.45 amol.cell-1.h-1), which was similar in CHF myocytes. These findings sug...Continue Reading

Citations

Aug 24, 2000·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·A LuchnerJ C Burnett
May 31, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Teruo NoguchiMartin M LeWinter
Jun 15, 2007·Physiology·Misuk KangJeffery W Walker
May 17, 2001·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·J L LiuI H Zucker
Jul 17, 2001·American Journal of Physiology. Heart and Circulatory Physiology·M L CokerF G Spinale
Jun 14, 2005·American Journal of Physiology. Heart and Circulatory Physiology·D KonradM Haney
Jan 21, 2011·Physiological Reviews·Donald E KohanDavid M Pollock
Aug 12, 2000·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·P KinnunenH Ruskoaho
Apr 3, 2007·American Journal of Physiology. Heart and Circulatory Physiology·D KonradA Oldner
Jun 14, 2000·American Journal of Physiology. Heart and Circulatory Physiology·A ErgulF G Spinale
Nov 14, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Sophie MotteKathleen McEntee

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