Decreased nitric oxide availability contributes to acute cerebral ischemia after subarachnoid hemorrhage.
OBJECTIVE
Disturbances of the L-arginine-nitric oxide (NO) vasodilatory pathway have been implicated as a cause of acute vasoconstriction and ischemia after subarachnoid hemorrhage (SAH). Because NO-dependent vasodilatory mechanisms are still intact in this setting, acute vasoconstriction may be the result of limited NO availability after SAH. The present study examines this hypothesis by administration of the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME).


METHODS
SAH was induced by the endovascular suture method in anesthetized rats. L-NAME (30 mg/kg intravenously) was injected 20 minutes before or 15, 30, or 60 minutes after SAH. Control rats received normal saline. Arterial and intracranial pressure and cerebral blood flow (CBF) were measured continuously for 60 minutes after SAH.


RESULTS
L-NAME administration 20 minutes before SAH produced a significant decrease in resting CBF (29.4 +/- 3.4%; P < 0.05), but it had no effect on the acute decrease in CBF after SAH or on its early recovery up to 30 minutes after SAH. However, a significant decrease in CBF recovery was found in animals receiving L-NAME injections (28.7 +/- 9.4%; P < 0.05 versus controls) 60 minutes after SAH. Administration of L-NAME 15 or 30 minutes after SAH had no effect on CBF recovery, as compared with controls. However, when administered 60 minutes after SAH, L-NAME decreased CBF significantly (45.4 +/- 8.8%; P < 0.05 versus controls).


CONCLUSIONS
These results indicate a biphasic pattern of NO availability after SAH. NO-mediated vasodilation is limited during the first 30 minutes of SAH and is restored 60 minutes after SAH.
Department of Neurosurgery, Mount Sinai School of Medicine, New York, New York 10029, USA.
A Y
AY
Schwartz
F A
FA
Sehba
J B
JB
Bederson
D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000209:etiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000172:deficiency*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013345:Subarachnoid Hemorrhage / Q000150:complications*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester