Combined effect of L-arginine and superoxide dismutase on the spastic basilar artery after subarachnoid hemorrhage in dogs.
To investigate the function of nitric oxide (a major endothelium-derived relaxing factor) in cerebral arteries after subarachnoid hemorrhage (SAH) in vivo, several nitric oxide-related substances were administered to dogs that had undergone double SAH. These included L-arginine (a substrate for the formation of nitric oxide), NG-monomethyl-L-arginine (L-NMMA, an analog of L-arginine that inhibits the formation of nitric oxide from L-arginine), and superoxide dismutase (SOD, which protects nitric oxide from oxidation by superoxide anion), which were given via intracisternal injection. The diameter of the basilar artery was assessed angiographically. In intact dogs, intracisternal bolus injections of L-arginine (1, 10, or 100 mumol) produced a dose-dependent increase in the internal diameter of the basilar artery; conversely, L-NMMA reduced the diameter of the basilar artery from baseline in a dose-dependent manner. On Days 4 and 7, after two intracisternal injections of autologous blood, L-arginine produced transient vasodilation of the spastic basilar artery, whereas L-NMMA produced no significant vasoconstriction. The vasodilator effect of L-arginine after SAH was stronger on Day 4 than on Day 7, but less than in intact dogs. Intracisternal injection of SOD, which caused no effect per se, enhanced the duration of the vasodilator effect of L-arginine on the basilar artery on Day 4 and both the magnitude and duration of that effect on Day 7. Thus, the basal release of nitric oxide was impaired after SAH, but the ability to synthesize nitric oxide in the vascular wall was not abolished. The finding that the simultaneous injection of SOD enhanced and prolonged the vasodilation induced by sufficient exogenous L-arginine suggests that the inactivation of nitric oxide by superoxide anion contributes to the development of vasospasm.
Kajita
Y
Y
Department of Neurosurgery, Nagoya University School of Medicine, Japan.
Suzuki
Y
Y
Oyama
H
H
Tanazawa
T
T
Takayasu
M
M
Shibuya
M
M
Sugita
K
K
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism*; D004285:Dogs; D005260:Female; D002546:Ischemic Attack, Transient / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D013482:Superoxide Dismutase