Vasodilator actions of flunarizine in isolated dog cerebral and extracerebral arteries.
Flunarizine relaxed isolated canine arteries precontracted with prostaglandin (PG) F2 alpha, epithio-methano-thromboxane A2 and K+; the relaxation was in the order of cerebral greater than renal greater than mesenteric = coronary arteries, when contracted with PGF2 alpha or the thromboxane A2 analogue. Flunarizine-induced relaxation was unaffected by treatment with atropine, propranolol, cimetidine, cimetidine, chlorpheniramine, aminophylline and indomethacin, and by removal of endothelium. Under normoxia, flunarizine attenuated contractions elicited by Ca2+ in the K+-stimulated cerebral and mesenteric arteries that had been previously exposed to Ca2+-free media to a greater extent than that in PGF 2 alpha-stimulated preparations. The Ca2+-induced contraction in cerebral arteries was more sensitive to flunarizine than that in mesenteric arteries. Contractions caused by PGF2 alpha in Ca2+-free media were not influenced by flunarizine. In cerebral and mesenteric arteries that had been previously exposed to Ca2+-free media and severe hypoxia and then stimulated by PGF2 alpha and Ca2+, reoxygenation produced a persistent contraction. Flunarizine suppressed the reoxygenation induced-contraction. It is concluded that flunarizine dilates cerebral arteries predominantly over the other arteries; the vasodilatation appears to derive from an interference with the transmembrane Ca2+ influx that occurs through a voltage-dependent process and, to a lesser extent, receptor-operated channels, but not with the Ca2+ release from stored sites. Contraction induced by reoxygenation is expected to be due mainly to the transmembrane influx of Ca2+, which is also suppressed by flunarizine.
Bian
K
K
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Toda
N
N
D000818:Animals; D001158:Arteries / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005444:Flunarizine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010100:Oxygen / Q000502:physiology; D011188:Potassium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D015237:Dinoprost; D005444:Flunarizine; D011188:Potassium; D010100:Oxygen; D002118:Calcium