Effects of CD-349, a dihydropyridine derivative, on contraction induced by vasoactive agents in canine basilar artery after subarachnoid hemorrhage.
We investigated the effects of CD-349, a dihydropyridine derivative, on contraction induced by vasoactive agents in canine basilar artery after subarachnoid hemorrhage (SAH). Ca(2+)-induced contraction of basilar arterial strips preincubated with serotonin (5-HT, 3x10(-6)M) was potentiated in strips from SAH. However, Ca(2+)-induced contraction of arterial strips which were depolarized with isotonic K+ (64mM) was attenuated in strips from SAH. These Ca(2+)-induced contractions of the basilar arteries preincubated with 5-HT and K+ from both control and SAH dogs were significantly inhibited by CD-349 and nicardipine, both dihydropyridine derivatives. 5-HT contracted the basilar arterial strips in a concentration-dependent manner; however, the maximal contraction of the basilar arterial strips to 5-HT was enhanced in SAH. Endothelium-dependent relaxation in response to substance-P was attenuated in SAH when compared to that in control dogs. Early treatment with CD-349 (1 or 2mg/kg/day, i.m.) for 1 week reversed not only the enhanced contraction of the basilar artery in response to 5-HT but also the impairment of endothelium-dependent relaxation in response to substance-P in SAH. It is expected that CD-349 may be a useful agent for the treatment of cerebrovascular diseases such as SAH.
Kamata
K
K
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Nishiyama
H
H
Miyata
N
N
Kasuya
Y
Y
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000503:physiopathology; D002118:Calcium / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009529:Nicardipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy* / Q000503:physiopathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D004095:Dihydropyridines; D012701:Serotonin; C054179:CD 349; D009529:Nicardipine; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium; D008751:Methylene Blue