Inotropic response of rabbit ventricular myocytes to endothelin-1: difference from isolated papillary muscles.
Endothelin-1 (ET-1) increased cell shortening and Ca2+ transients over the concentration of 3 x 10(-11) M to 10(-9) M with EC50 of 8.3 x 10(-11) M in rabbit single ventricular myocytes. Thus ET-1 was approximately 60 times more potent in single myocytes than in papillary muscles (EC50 = 5.1 x 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.
Talukder
M A
MA
Department of Pharmacology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
Norota
I
I
Sakurai
K
K
Endoh
M
M
D000818:Animals; D004594:Electrophysiology; D019332:Endothelin-1 / Q000494:pharmacology*; D006352:Heart Ventricles / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D009928:Organ Specificity; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D011817:Rabbits; D016276:Ventricular Function
D019332:Endothelin-1