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.
Okumura
K
K
New Drug Research Laboratory, Maruko Pharmaceutical Co., Ltd., Kasugai, Japan.
Ichihara
K
K
Nagasaka
M
M
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D011169:Portal Vein / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; C059427:aranidipine; D011189:Potassium Chloride