Effects of endothelin-1 on the contractility of cardiomyocytes from the spontaneously hypertensive rat.
1. Disturbances in cardiovascular responsiveness to endogenous endothelin-1 (ET-1) may play a significant role in the pathogenesis of essential hypertension. In this study the inotropic responses of cardiomyocytes derived from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rat (SHR) strains to ET-1 (10(-11)-10(-8) mol/L) were characterized. Isotonic contraction cycles of ventricular cardiomyocytes isolated from age-matched (11 week) WKY and SHR rats were recorded using a rapid digital imaging technique and evaluated by computation of a range of normalized parameters. 2. The maximum effect of ET-1, eliciting a 60-70% increase in myocyte shortening after 3 min, was observed at 10(-9) mol/L in both strains, and was associated with elevations in the rate of shortening and lengthening, abbreviated latency, contractile cycle prolongation and delayed time to peak shortening. 3. No evidence for a significant strain dependent difference in the relative responsiveness to ET-1 was detected. This finding indicates that altered sensitivity to ET-1 is unlikely to be a major factor underlying the development of hypertension in this model. 4. The distinct nature of the alterations in contractile parameters produced by ET-1 compared with angiotensin II (AII) suggests that the prevailing cellular mechanisms of action of these peptides are different and that ET-1 is not a paracrine or autocrine inotropic intermediate for AII.
Delbridge
L M
LM
Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
Morgan
T O
TO
Harris
P J
PJ
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D007551:Isotonic Contraction / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D016232:Endothelins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II