Vasoinhibitory effect of NP-252, a new dihydropyridine derivative, in canine cerebral artery.
The vasoinhibitory effect of NP-252, a 1,4-dihydropyridine derivative Ca++ antagonist, was examined in canine cerebral artery, and this effect was compared with that of nifedipine. NP-252 (10(-7)M) and nifedipine (10(-6) M) nearly abolished the contraction induced by addition of Ca++ to Ca(++)-free medium containing KC1. NP-252 (10(-6)M) and nifedipine (10(-6)M) attenuated the contraction produced by thromboxane A2 agonist (STA2) in normal medium, and the resultant contractions were 22% (n = 6) and 35% (n = 6) of the control contraction, respectively. The vasoinhibitory effects of NP-252 were significantly stronger than those of nifedipine in canine cerebral artery. NP-252 (10(-7) and 10(-6) M) dose-dependently attenuated nifedipine-resistant Ca(++)-contraction in the presence of STA2 in both canine cerebral and coronary arteries. The inhibitory effect of combined treatment with NP-252 (10(-6) M) and nitroglycerin (10(-6) M) on nifedipine-resistant Ca(++)-contraction in the cerebral artery was additive. These results indicate that NP-252 possesses a stronger vasoinhibitory effect than that of nifedipine in canine cerebral artery.
Akimoto
Y
Y
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
Kurahashi
K
K
Usui
H
H
Fujiwara
M
M
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology
D004095:Dihydropyridines; C067290:NP 252; D013928:Thromboxane A2; D011189:Potassium Chloride; C037866:STA 2; D009543:Nifedipine; D002118:Calcium