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

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Abstract
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