Endothelin has potent direct inotropic and chronotropic effects in cultured heart cells.
To determine whether endothelin, a highly potent vasoconstrictor peptide, may affect cardiac myocyte contractility directly, we studied the effects of synthetic porcine endothelin-1 in cultured chick embryo ventricular cells. Endothelin-1 had a potent chronotropic effect (EC50 0.17 nmol/l) in spontaneously beating cells. The increase in the beating rate was accompanied by a frequency-dependent decrease in the amplitude of contraction. In electrically driven cells (1 Hz), endothelin-1 increased the amplitude of contraction dose-dependently, with an EC50 of 0.3 nmol/l, smaller than that of the calcium channel blocker BAY K 8644 (EC50 3.3 nmol/l), and with an efficacy close to that of BAY K 8644 and isoproterenol. Nicardipine (100 nmol/l) shifted to the right, by two orders of magnitude, the dose-response curve of endothelin-1 for inotropism. These results indicate that endothelin-1 is one of the most potent inotropic agents in cultured cardiac myocytes, and suggest that this effect involves, at least in part, a calcium ion influx through voltage-sensitive calcium channels.
Concas
V
V
Laboratory of Cardiovascular Pharmacology, University Broussals-Hôtel Dieu, Paris, France.
Laurent
S
S
Brisac
A M
AM
Perret
C
C
Safar
M
M
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D016232:Endothelins; D004730:Endothelium, Vascular / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D013268:Stimulation, Chemical
D015220:Calcium Channels; D016232:Endothelins; D010455:Peptides