Decreased nitric oxide availability contributes to acute cerebral ischemiaafter subarachnoid hemorrhage

OBJECTIVE: Disturbances of the L-arginine-nitric oxide (NO) vasodilatory pa thway have been implicated as a cause of acute vasoconstriction and ischemi a after subarachnoid hemorrhage (SAH). Because NO-dependent vasodilatory me chanisms ave still intact in this setting, acute vasoconstriction may be th e result of limited NO availability after SAH. The present study examines t his hypothesis by administration of the NO synthase inhibitor N-G-nitro-L-a rginine 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 cont inuously 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 minu tes 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 contro ls) 60 minutes after SAH. Administration of L-NAME 15 or 30 minutes after S AH 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). CONCLUSION: These results indicate a biphasic pattern of NO availability af ter SAH. NO-mediated vasodilation is limited during the first 30 minutes of SAH and is restored 60 minutes after SAH.