EFFECTS OF ENDOTHELIN-1 ON THE CONTRACTILITY OF CARDIOMYOCYTES FROM THE SPONTANEOUSLY HYPERTENSIVE RAT

1. Disturbances in cardiovascular responsiveness to endogenous endothe lin-1 (ET-1) may play a significant role in the pathogenesis of essent ial hypertension. In this study the inotropic responses of cardiomyocy tes derived from normotensive Wistar-Kyoto (WKY) and spontaneously hyp ertensive rat (SHR) strains to ET-1 (10(-11)-10(-8) mol/L) were charac terized. Isotonic contraction cycles of ventricular cardiomyocytes iso lated from age-matched (11 week) WKY and SHR rats were recorded using a rapid digital imaging technique and evaluated by computation of a ra nge 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 th e rate of shortening and lengthening, abbreviated latency, contractile cycle prolongation and delayed time to peak shortening. 3. No evidenc e for a significant strain dependent difference in the relative respon siveness to ET-1 was detected. This finding indicates that altered sen sitivity to ET-1 is unlikely to be a major factor underlying the devel opment of hypertension in this model. 4. The distinct nature of the al terations in contractile parameters produced by ET-1 compared with ang iotensin II (AII) suggests that the prevailing cellular mechanisms of action of these peptides are different and that ET-1 is not a paracrin e or autocrine inotropic intermediate for AII.