Developmental changes of effects of endothelins in rat hearts

• Published in: Japanese Journal of Pharmacology 1990, Vol.52 (suppl-1.1), p.280-280
• Main Authors: Tomohisa Ishikawa, Liming Li, Osamu Shinmi, Sadao Kimura, Masashi Yanagisawa, Katsutoshi Goto, Tomoh Masaki
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, which is produced in the vascular endothelial cells. In addition to its effect on the vascular smooth muscles, we have demonstrated that ET-1 exerts positive inotropic and chronotropic effects on the guinea pig atria. In the present study, we investigated the effects of ET-1 and endothelin-3 (ET-3), which is an isoform of ET-1, on the cardiac muscles of neonatal (5 to 7 days old) and adult (8 weeks old) rats in vitro. ET-1 and ET-3 caused dose-dependent, positive inotropic and chronotropic responses in the isolated atria of both neonatal and adult rats. Interestingly, in the ventricular muscle sections of neonatal rats, but not in those of adult rats, ET-1 and ET-3 induced positive inotropic responses. In contrast, Bay K 8644, an L-type calcium channel agonist, exerted positive inotropic actions on both neonatal and adult ventricles. These results suggest that the endothelin receptors and/or the mechanisms for the endothelin-induced inotropic response in the rat ventricular muscle specifically diminish during development. We are now investigating the characteristics of endothelin receptors using receptor binding assays for ET-1 and ET-3.