Effects of aranidipine, a novel calcium channel blocker, on mechanical responses of the isolated rat portal vein: comparison with typical calcium channel blockers and potassium channel openers.

We investigated the effects of aranidipine, a dihydropyridine-type Ca2+ channel blocker, on contractile responses to KCl and spontaneous contractions in isolated rat portal veins in comparison with those of the Ca2+ channel blockers, nifedipine, nicardipine, nitrendipine, diltiazem, and verapamil, and of the K+ channel openers, cromakalim and nicorandil. All the Ca2+ channel blockers concentration-dependently inhibited contractions induced by KCl. Interestingly, aranidipine was more potent against the low K+ (20 mM)-induced contraction than the high K+ (80 mM)-induced contraction, whereas the other Ca2+ channel blockers were equally potent against contractions induced by either concentration of KCl. Cromakalim and nicorandil were effective only on the low K(+)-induced contraction. In addition, all the Ca2+ channel blockers and the K+ channel openers tested inhibited the amplitude of spontaneous contractions of isolated rat portal vein. Tetraethylammonium (TEA), a classic K+ channel blocker, significantly attenuated the effect of aranidipine but not of other Ca2+ channel blockers on the spontaneous contractions. The cromakalim-induced inhibition of spontaneous contractions was antagonized by TEA. Thus aranidipine was found to be different from the typical Ca2+ channel blockers and in part similar to the K+ channel openers in inhibiting mechanical responses of isolated rat portal vein, suggesting that activation of K+ channels may in part in part be involved in the aranidipine-induced vasodilation.