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.