Effects of S-nitrosoglutathione on acute vasoconstriction and glutamate release after subarachnoid hemorrhage

Background and Purpose-Subarachnoid hemorrhage (SAH) causes acute vasoconst riction that contributes to ischemic brain injury shortly after the initial bleed. It has been theorized that decreased availability of nitric oxide ( NO) may contribute to acute vasoconstriction. Therefore we examined the eff ect of the NO donor N-nitroso glutathione (GSNO) on acute vasoconstriction and early ischemic glutamate release after experimental SAH. Methods-SAH was induced by the endovascular suture method in anesthetized r ats. GSNO (1 mu mol/L/kg, n = 31) or saline (n = 21) was injected 5 minutes after SAH, Sham-operated rats received GSNO (1 mu mol/L/kg, n = 5) 5 minut es after sham surgery. Arterial and intracranial pressures, cerebral blood flow (CBF), and extracellular glutamate release were measured serially for 60 minutes after SAH, SAH size was determined, and vascular measurements we re made histologically. Results-GSNO had no effect on resting blood pressure, intracranial pressure , cerebral perfusion pressure, or CBF in sham-operated animals. However, ad ministration of GSNO after SAH was associated with significantly increased CBF (161.6 +/- 26.6% versus saline 37.1 +/- 5.5%, 60 minutes after SAH, P<0 .05), increased blood vessel diameter (internal carotid artery [ICA] 285.0 +/- 16.5 mu m versus saline 149.2 +/- 14.1 mu m, P<0.01), decreased vessel wall thickness (ICA12.9 +/- 0.7 mu m versus saline 25.1 +/- 1.6 mu m, P<0.0 1), and decreased extracellular glutamate levels (3315.6 +/- 1048.3% versus saline 469.7 +/- 134.3%, P<0.05), Blood pressure decreased transiently, wh ereas intracranial pressure, cerebral perfusion pressure, and SAH size were not affected, Conclusions-These results suggest that GSNO can reverse acute vasoconstrict ion and prevent ischemic brain injury after SAH. This further implies that acute vasoconstriction contributes significantly to ischemic brain injury a fter SAH and is mediated in part by decreased availability of NO.