Effects of benidipine hydrochloride on contractions induced by some contractile agents in isolated cerebral and mesenteric arteries of dogs.
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)
Suzuki
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
Uegomori
T
T
Ozaki
S
S
Takata
Y
Y
Kato
H
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009529:Nicardipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; D012701:Serotonin; C061004:benidipine; D013928:Thromboxane A2; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D009529:Nicardipine