Dual role of endothelin-1 via ETA and ETB receptors in regulation of cardiac contractile function in mice

Jarkko Piuhola, Markus Mäkinen, I. Szokodi, Heikki Ruskoaho

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

An increase in coronary perfusion pressure leads to increased cardiac contractility, a phenomenon known as the Gregg effect. Exogenous endothelin (ET)-1 exerts a positive inotropic effect; however, the role of endogenous ET-1 in the contractile response to elevated load is unknown. We characterized here the role of ETA and ETB receptors in regulation of contractility in isolated, perfused mouse hearts subjected to increased coronary flow. Elevation of coronary flow from 2 to 5 ml/min resulted in 80 ± 10% increase in contractile force (P <0.001). BQ-788 (ETB receptor antagonist) augmented the load-induced contractile response by 35% (P <0.05), whereas bosentan (ETA/B receptor antagonist) and BQ-123 (ETA receptor antagonist) attenuated it by 34% and 56%, respectively (P <0.05). CV-11974 (ANG II type 1 receptor antagonist) did not modify the increase in contractility. These results show that endogenous ET-1 is a key mediator of the Gregg effect in mouse hearts. Moreover, ET-1 has a dual role in the regulation of cardiac contractility: ETA receptor-mediated increase in contractile force is suppressed by ETB receptors.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number1 54-1
Publication statusPublished - Jul 1 2003

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Endothelin-1
Perfusion
Pressure

Keywords

  • Angiotensin II
  • Coronary pressure
  • Gregg effect

ASJC Scopus subject areas

  • Physiology

Cite this

Dual role of endothelin-1 via ETA and ETB receptors in regulation of cardiac contractile function in mice. / Piuhola, Jarkko; Mäkinen, Markus; Szokodi, I.; Ruskoaho, Heikki.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 285, No. 1 54-1, 01.07.2003.

Research output: Contribution to journalArticle

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