Biphasic inotropic response to endothelin-1 in the presence of various concentrations of norepinephrine in dog ventricular myocardium.
The present study was undertaken to investigate the interaction between endothelin-1 (ET-1) and norepinephrine (NE) on contractile regulation in dog ventricular myocardium. ET-1 alone did not elicit any inotropic response in isolated dog ventricular trabeculae (37 degrees C, 0.5 Hz). In the presence of NE at a high concentration (10(-7) M), ET-1 (10(-8) M) elicited a long-lasting negative inotropic effect, while in the presence of NE at a moderate concentration (3 x 10(-8) M) it produced a biphasic inotropic effect: a sustained positive inotropic effect subsequent to a short-lasting negative inotropic effect. In the presence of a lower concentration (10(-9) M) that affected scarcely the basal force of contraction, ET-1 produced a pronounced positive inotropic effect in association with negative lusitropic and negative clinotropic effects in a concentration-dependent manner subsequent to a small transient negative inotropic effect. The presented results indicate that not only the extent, but also the quality of the inotropic response to ET-1 is determined by the level of NE in the biophase. The crosstalk of ET-1 with NE may play a crucial role in pathophysiological regulation of cardiac contractility in intact dog ventricular myocardium.
Chu
L
L
Department of Pharmacology, Yamagata University School of Medicine, Japan.
Endoh
M
M
D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D006352:Heart Ventricles; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D019332:Endothelin-1; D010566:Virulence Factors, Bordetella; D009638:Norepinephrine