Inhibition by calmodulin antagonists of the neurogenic relaxation in cerebral arteries.
The present study was aimed to determine the effect of calmodulin inhibitors on the relaxant response of isolated dog and monkey cerebral arteries to vasodilator nerve stimulation, which is hypothesized to be mediated by nitric oxide (NO) from nerve endings. The relaxations caused by nerve stimulation by electrical pulses in endothelium-denuded arteries were attenuated by treatment with calmidazolium and W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide hydrochloride) and were abolished by NG-nitro-L-arginine, an inhibitor of nitric oxide synthase, and tetrodotoxin. The calmodulin inhibitors also attenuated the relaxations caused by nicotine and substance P, which were endothelium-independent and -dependent, respectively, but did not influence the relaxant response to NO. It is concluded that calmodulin is required for activation of the NO synthase present in the vasodilator nerve as well as that in the endothelium.
Okamura
T
T
Department of Pharmacology, Shiga University of Medical Science, Ohtsu, Japan.
Toda
N
N
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002536:Cerebral Arteries / Q000187:drug effects / Q000294:innervation; D004285:Dogs; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008251:Macaca; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000294:innervation; D009538:Nicotine / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D019335:Nitroarginine; D013373:Substance P / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology
D002147:Calmodulin; D007093:Imidazoles; D013449:Sulfonamides; D019335:Nitroarginine; D009569:Nitric Oxide; D013373:Substance P; C031938:calmidazolium; C017967:W 7; D009538:Nicotine; D001120:Arginine