1995 年 18 巻 4 号 p. 507-513
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 (3×10-10-3×10-6M) and 5-hydroxytryptamine (5-HT) (10-9-3×10-6M) produced concentration-dependent contractions in the three arteries. Benidipine (10-11-8×10-9M) 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 cerbral and mesenteric arteries. Benidipine (10-6-3×10-5M) 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 Ca2+-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 10-6M U-46619 and 3×10-6M 5-HT in the cerebral and mesenteric arteries by 56-61 and 34-39%, respectively. These results suggest that the more effective inhibition of KCl-induced contractions by benidipine, as well as nicardipine, in the cerebral arteries may be due to a greater dependence of the KCl-induced contraction in the cerebral arteries on extracellular Ca2+, compared with the mesenteric arteries.
