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

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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.

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