Inhibition of histamine-induced Ca2+ efflux in cultured vascular smooth muscle cells by an antihypertensive drug, cicletanine.

The effect of cicletanine, a new antihypertensive drug, on histamine-induced Ca2+ release in cultured vascular smooth muscle cells from guinea-pig aorta was examined. In 45Ca2+ labelled cells, histamine increased in a dose-dependent manner the Ca2+ efflux (EC50 = 8 x 10(-6) M). This stimulation of 45Ca2+ efflux was also observed with an H1-agonist [2-pyridylethylamine dihydrochloride (2-PEA)] but not with an H2-agonist (dimaprit). Histamine- or 2-PEA-induced 45Ca2+ efflux was inhibited by an H1-antagonist (mepyramine), whereas an H2-antagonist (cimetidine) had no effect. Cicletanine was as effective as the H1-antagonist in inhibiting histamine- or 2-PEA-stimulated 45Ca2+ efflux in a dose-dependent manner (IC50 = 10(-6) M). Only the racemic form and the R(-) enantiomer of cicletanine behaved as histaminergic antagonists, the S(+) enantiomer having no effect. These results suggest that the direct effect of cicletanine on the mobilization of Ca2+ by blocking H1-receptors may participate in an antihypertensive mechanism by producing relaxation of blood vessels.