Akimoto Y, Kurahashi K, Usui H, Fujiwara M
Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.
Life Sci. 1991;48(2):183-8. doi: 10.1016/0024-3205(91)90412-5.
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.
研究了1,4 - 二氢吡啶衍生物钙拮抗剂NP - 252对犬脑动脉的血管抑制作用,并将其与硝苯地平的作用进行了比较。NP - 252(10⁻⁷M)和硝苯地平(10⁻⁶M)几乎完全消除了在含氯化钾的无钙培养基中加入钙离子所诱导的收缩。NP - 252(10⁻⁶M)和硝苯地平(10⁻⁶M)减弱了正常培养基中血栓素A2激动剂(STA2)所产生的收缩,所产生的收缩分别为对照收缩的22%(n = 6)和35%(n = 6)。在犬脑动脉中,NP - 252的血管抑制作用明显强于硝苯地平。在犬脑动脉和冠状动脉中,NP - 252(10⁻⁷和10⁻⁶M)在存在STA2的情况下剂量依赖性地减弱了硝苯地平耐药性钙离子收缩。NP - 252(10⁻⁶M)与硝酸甘油(10⁻⁶M)联合治疗对脑动脉中硝苯地平耐药性钙离子收缩的抑制作用是相加的。这些结果表明,在犬脑动脉中,NP - 252具有比硝苯地平更强的血管抑制作用。