Cardiodepressive and noradrenaline-antagonistic effects of the organic calcium-antagonist D 600 in the spontaneously beating guinea-pig atrium
Wagner, J.; Schümann, H.J.
Archives Internationales de Pharmacodynamie et de Therapie 229(2): 206-212
1977
ISSN/ISBN: 0003-9780 PMID: 596975 Document Number: 119568
The influence of the organic Ca-antagonist D 600 for the positive chronotropic effect of noradrenaline was not influenced over the concentration range of 10-9 to 10-7 M. The pD2-value for the positive inotropic effect of noradrenaline was diminished by 10-9 M D 600 with 0.33 log units. Higher concentrations up to 3 .times. 10-8 M did not alter the pD2-value, indicating a functional type of antagonism. D 600 exerted a negative inotropic and chronotropic effect only in concentrations of 3 .times. 10-8 and 10-7 M; lower concentrations proved ineffective. After pretreatment with reserpine, 10-9 and 10-8 M D 600 caused a cardiodepressive effect. Noradrenaline (3 .times. 10-9 M), which did not cause any positive inotropic effect in this concentration, decreased the sensitivity towards 10-9 and 10-8 M D 600 in the electrically driven left atrium. The low sensitivity for D 600 seen in the spontaneously beating atrium might be explained by the liberation of endogenous noradrenaline during sinus node activity. A sympathetic counterregulation against the effect of Ca-antagonists is suggested.