Vasodilatory properties in vascular smooth muscle of the calcium antagonist NB-818 compared to nicardipine and nimodipine.
The vasodilatory properties of NB-818 were compared with those of nicardipine and nimodipine. NB-818 produced a greater attenuation of 50 mM KCl-induced contraction in the basilar than in the coronary or mesenteric arteries. The time-course of the relaxation of KCl-induced vasocontraction produced by NB-818 was statistically significantly slower than that produced by nicardipine and nimodipine. The response of the basilar artery to KCl after NB-818 washout was statistically significantly slower than the response of the coronary and mesenteric arteries. The response after nicardipine or nimodipine washout did not differ from that in the other arteries. In canine vessels, NB-818, nicardipine and nimodipine shifted the concentration-response curve for CaCl2 to the right and diminished the maximal responses. When compared with IC50 values obtained from the concentration-response curve at 3 mM CaCl2, NB-818 was 5.3 times more potent on basilar than on mesenteric arteries, whereas both nicardipine and nimodipine showed similar potency in the two arteries. NB-818 inhibited both the 45Ca-uptake and the contraction induced by 55.4 mM KCl in a concentration-dependent manner, whereas as concerns the 45Ca-uptake and the contraction induced by 10(-5) norepinephrine, NB-818 slightly inhibited the former but not the latter. These results suggest that the vasodilatory properties of NB-818 may be different from those of nicardipine and nimodipine; that is, in showing very slow rates of onset and offset of action on the basilar artery, actions which are attributed mainly to inhibition of calcium influx through potential-operated calcium channels.
Nishikibe
M
M
Central Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Fukuroda
T
T
Nakajima
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology; D002132:Calcium Radioisotopes; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009529:Nicardipine / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D002121:Calcium Channel Blockers; D002132:Calcium Radioisotopes; D004095:Dihydropyridines; D009553:Nimodipine; D011189:Potassium Chloride; C048962:NPK 1886; D009529:Nicardipine; D002122:Calcium Chloride; D002118:Calcium