Suzuki S, Uegomori T, Ozaki S, Takata Y, Kato H
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Biol Pharm Bull. 1995 Apr;18(4):507-13. doi: 10.1248/bpb.18.507.
The effects of benidipine on contractions induced by contractile agents were studied in isolated dog basilar, middle cerebral and mesenteric arteries and compared with those of nicardipine. KCl (20-80 mM), U-46619 (3 x 10(-10)-3 x 10(-6)M) and 5-hydroxytryptamine (5-HT) (10(-9)-3 x 10(-6)M) produced concentration-dependent contractions in the three arteries. Benidipine (10(-11)-8 x 10(-9)M) inhibited non-competitively the KCl-induced contraction in the basilar, middle cerebral and mesenteric arteries with a pD'2 of 9.1, 9.7 and 8.5, respectively. There was a significant difference between the pD'2 values in the cerebral and mesenteric arteries. Benidipine (10(-6)-3 x 10(-5)M) attenuated significantly the contraction produced by both U-46619 and 5-HT in the three arteries, the pD'2 being 4.4-4.9. Nicardipine inhibited the contraction induced by the three contractile agents in the same manner as benidipine. The contraction caused by 70 mM KCl in the cerebral and mesenteric arteries was reduced by 33-38 and 18%, respectively following treatment with 0.25 mM Ca2+ solution. Furthermore, pretreatment with a Ca(2+)-free solution containing 1 mM EGTA inhibited KCl-induced contractions in the basilar, middle cerebral and mesenteric arteries by 98.7, 95.6 and 92.1%, respectively. It also attenuated the contractions produced by both 10(-6) M U-46619 and 3 x 10(-6) M 5-HT in the cerebral and mesenteric arteries by 56-61 and 34-39%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
在离体犬基底动脉、大脑中动脉和肠系膜动脉中研究了贝尼地平对收缩剂诱导的收缩作用，并与尼卡地平进行了比较。氯化钾（20 - 80 mM）、U - 46619（3×10⁻¹⁰ - 3×10⁻⁶ M）和5 - 羟色胺（5 - HT）（10⁻⁹ - 3×10⁻⁶ M）在这三种动脉中产生浓度依赖性收缩。贝尼地平（10⁻¹¹ - 8×10⁻⁹ M）非竞争性抑制基底动脉、大脑中动脉和肠系膜动脉中氯化钾诱导的收缩，其pD'₂分别为9.1、9.7和8.5。大脑中动脉和肠系膜动脉的pD'₂值存在显著差异。贝尼地平（10⁻⁶ - 3×10⁻⁵ M）显著减弱了U - 46619和5 - HT在这三种动脉中产生的收缩，pD'₂为4.4 - 4.9。尼卡地平以与贝尼地平相同的方式抑制这三种收缩剂诱导的收缩。用0.25 mM钙离子溶液处理后，大脑中动脉和肠系膜动脉中70 mM氯化钾引起的收缩分别降低了33 - 38%和18%。此外，用含1 mM乙二醇双四乙酸的无钙溶液预处理分别抑制了基底动脉、大脑中动脉和肠系膜动脉中氯化钾诱导的收缩98.7%、95.6%和92.1%。它还分别减弱了大脑中动脉和肠系膜动脉中10⁻⁶ M U - 46619和3×10⁻⁶ M 5 - HT产生的收缩56 - 61%和34 - 39%。（摘要截于250字）
