Modulation of extraluminally induced vasoconstrictions by endothelium-derived nitric oxide in the canine basilar artery.
The present study was undertaken to investigate the role of endothelium in extraluminally induced vasospasm of the cerebral artery using isolated perfused canine basilar arteries. The extraluminal applications of high K+ and prostaglandin F2 alpha (PGF2 alpha) induced concentration-dependent vasoconstriction. Both constrictive responses were significantly enhanced by denuding endothelium. Additionally, the responses in the endothelium-intact arteries were markedly augmented by intraluminal perfusion with NG-monomethyl-L-arginine (L-NMMA). These results suggest that the inhibition of nitric oxide (NO) synthase in endothelium enhances increase in transmembrane Ca(2+)-influx which is a common constrictive mechanism to the vasoconstrictors. The augmentative action induced by L-NMMA was inhibited by intraluminal perfusion of L-arginine, but not by D-arginine. Furthermore, the augmentation was not observed in the arteries without endothelium. These results suggest that the endothelium may have a great significance on responsiveness to extraluminal vasoactive substances and that endothelium-derived NO may modulate the extraluminally induced vasoconstriction which is responsible for cerebral vasospasm after subarachnoid hemorrhage.
Minato
H
H
Department of Pharmacology, Dainippon Pharmaceutical Co. Ltd., Osaka, Japan.
Hashizume
M
M
Masuda
Y
Y
Hosoki
K
K
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001488:Basilar Artery / Q000187:drug effects* / Q000201:enzymology; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase; D011188:Potassium / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D015237:Dinoprost; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D011188:Potassium