Influence of hexobendine, prenylamine and verapamil on the contractile response of isolated rabbit left atria and aortae to calcium.

Abstract

Contraction was abolished by isolated rabbit left atria driven electrically at a frequency of 30/min, by increasing external K+ concentrations from 5.4 to 22 mM. Addition of isoproterenol (10-6M) restored the atrial contraction and the magnitude of contractions increased by raising external concentrations of Ca2+ to 4.4 and 6.6. mM. Hexobendine attenuated the magnitude of contractions restored by isoproterenol and excess Ca2+ in a dose-dependent manner, as did prenylamine and verapamil. Hexobendine did not significantly influence the membrane depolarization induced by excess K+ and there was no evidence of a .beta.-adrenergic blocking action. In helical strips of rabbit aortae exposed to Ca2+ free media and depolarized by excess K+, the addition of Ca2+ caused a marked contraction. Hexobendine, prenylamine and verapamil caused a dose-related attenuation of the Ca2+-induced contraction. Relative potencies of the inhibition by hexobendine, prenylamine and verapamil were 1:16.5:100. Inhibitory effects of these drugs were partially antagonized by excess Ca2+. Greater attenuation of the contractile response to 25 mM K+ than the response to 2 .times. 10-6 M noradrenaline [norepinephrine] was observed in preparations treated with hexobendine. Interference with the influx of Ca2+ across cell membrane in atrial muscles and aortic smooth muscles participates in the inhibition of contractility by hexobendine.