Inotropic response of rabbit ventricular myocytes to endothelin-1: difference from isolated papillary muscles

Department of Pharmacology, Yamagata University School of Medicine, Yamagata 990-9585, Japan Endothelin-1 (ET-1) increased cell shortening and Ca 2+ transients over the concentration of 3 × 10 11 M to 10 9 M with EC 50 of 8.3 × 10 11 M in rabbit single ventricular myocytes. Thus ET-1 was approximately 60 times more potent in single myocytes than in papillary muscles (EC 50 = 5.1 × 10 9 M) of the same species. In single myocytes, ET-1 at 10 8 M elicited an inhibitory response that counteracted the facilitatory response: the concentration-response curve (CRC) for ET-1 was bell shaped. The ET A -receptor antagonist BQ-485 shifted CRC for ET-1 to the right in parallel; however, the facilitatory response to 10 8 M ET-1 was markedly enhanced by BQ-485 and also by the ET B antagonist BQ-788. The ET A /ET B antagonist TAK-044 abolished the ET-1-induced response. These findings indicate that the response to ET-1 of single myocytes is different from that of papillary muscles in concentration dependence, characteristics of the response, and susceptibility to ET-receptor antagonists. Anomalous pharmacological characteristics of ET-1-induced response in rabbit papillary muscles may be due to integrated regulatory mechanisms that may involve also various types of noncardiac cell in ventricular myocardium. adult rabbit cardiomyocytes; cell shortening; Ca 2+ transients; ET A receptor; ET B receptor