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Am J Physiol Heart Circ Physiol (June 10, 2005). doi:10.1152/ajpheart.00892.2004
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Submitted on August 30, 2004
Accepted on May 31, 2005

Positive inotropic and negative lusitropic effects of endothelin receptor agonism in vivo

David Konrad1*, Anders Oldner1, Michael Wanecek1, Anders Rudehill1, Eddie Weitzberg1, Bjorn Biber2, Goran Johansson2, Soren Haggmark2, and Michael Haney2

1 Surgical Sciences, Karolinska Institute, Stockholm, Sweden
2 Perioperative and Surgical Sciences, Umea University, Umea, Sweden

* To whom correspondence should be addressed. E-mail: david.konrad{at}kirurgi.ki.se.

The endothelin (ET) system is involved in regulation of myocardial function in health as well as in several diseases such as congestive heart failure, myocardial infarction and septic myocardial depression. Conflicting results have been reported regarding the acute contractile properties of endothelin-1 (ET-1). We therefore investigated the effects of intra-coronary infusions of ET-1 and of the ETB-receptor selective agonist sarafotoxin 6c (S6c) with increasing doses in anaesthetized pigs. Myocardial effects were measured using analysis of left ventricular pressure-volume relationship. ET-1 elicited increases in myocardial contractile status (Ees 0.94±0.11 to 1.48±0.23, pre-load recruitable stroke work 68.7±4.7 to 83.4±7.2) that appear to be mediated through ETA-receptors whereas impairment in left ventricular isovolumic relaxation (tau 41.5±1.4 to 58,1±5.0 and pressure half time 23.0±0.7 to 30.9±2.6) was ETB-receptor dependent. In addition, intravenous administration of ET-1 impaired ventricular relaxation but had no effect on contractility. Intra-coronary S6c administration caused impairments in left ventricular relaxation (tau from 43.3±1.8 to 54.4±3.4) as well as coronary vasoconstriction. In conclusion, ET-1 elicits positive inotropic and negative lusitropic myocardial effects in a pig model, possibly resulting from ETA- and ETB-receptor activation respectively.




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Am. J. Physiol. Heart Circ. Physiol.Home page
D. Konrad, M. Haney, G. Johansson, M. Wanecek, E. Weitzberg, and A. Oldner
Cardiac effects of endothelin receptor antagonism in endotoxemic pigs
Am J Physiol Heart Circ Physiol, August 1, 2007; 293(2): H988 - H996.
[Abstract] [Full Text] [PDF]




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