Altered inotropic response of endothelin-1 in cardiomyocytes from rats with isoproterenol-induced cardiomyopathy

Open Access
Publisher Website
Google Scholar
Abstract
Objective: The positive inotropic effect of endothelin-1 (ET-1) on normal myocardial contraction may be altered in pathological states. The purpose of this study was to assess the direct effect of ET-1 on cardiomyocyte performance and its cellular mechanism in congestive heart failure (CHF). Methods: We measured the plasma levels of ET-1 and compared the effects of ET-1 (10−10–10−8 M) on contractile performance and the [Ca2+]i transient in the myocytes of left ventricles (LV) from 15 age-matched normal adult rats and 15 rats with isoproterenol (ISO)-induced CHF. Results: With CHF, the plasma levels of ET-1 (19.7±6.3 vs. 4.1±0.5 fmol/ml, pL/dtmax, 20–35%; p2+]i transient. In contrast, in myocytes from CHF rats, ET-1 produced significant reductions in SA (9–13%) and in the velocity of relengthening, dR/dtmax (10–14%; pR/dtmax also decreased by 8–10% (p2+]i transient (20–23%, pA receptor antagonist (BQ123) or a protein kinase C (PKC) inhibitor (H-7 or staurosporine). Conclusion: ISO-induced CHF is associated with elevated plasma ET-1 and an altered cardiomyocyte response to ET-1. After CHF, ET-1 produces a direct depression of cardiomyocyte contractile performance that is associated with a significant decrease in the peak [Ca2+]i transient. These effects are likely to be mediated through ETA receptors and involve the PKC pathway.

This publication has 0 references indexed in Scilit: