Acute decrease in cerebral nitric oxide levels after subarachnoid hemorrhage

Abstract

Disturbances in the nitric oxide (NO) vasodilatory pathway have been implicated in acute vasoconstriction and ischemia after subarachnoid hemorrhage (SAH). The authors hypothesize that blood released during SAH leads to vasoconstriction by scavenging NO and limiting its availability. This was tested by measuring the major NO metabolites nitrite and nitrate in five different brain regions before and after experimental SAH. The basal NO metabolites levels were as follows (mean ± SD, μmol/mg wet weight): brain stem, 0.14 ± 0.07; cerebellum, 0.12 ± 0.08; ventral convexity cortex, 0.22 ± 0.15; dorsal convexity cortex, 0,16 ± 0.11; and hippocampus, 0.26 ± 0.17. In sham-operated animals, no effect of the nitric oxide synthase (NOS) inhibitor L(G)-nitro-L-arginine-methyl-ester (30 mg/kg) was found on NO metabolites 40 minutes after administration, but a significant decrease was seen after 120 minutes. The NO metabolites decreased significantly 10 minutes after SAH in all brain regions except for hippocampus, and recovered to control levels in cerebellum at 60 minutes and in brain stem and dorsal cerebral cortex 180 minutes after SAH, while remaining low in ventral convexity cortex: Nitrite recovered completely in all brain regions at 180 minutes after SAH, whereas nitrate remained decreased in brain stem and ventral convexity cortex. Our results indicate that SAH causes acute decreases in cerebral NO levels by a mechanism other than NOS inhibition and provide further support for the hypothesis that alterations in the NO vasodilatory pathway contribute directly to the ischemic insult after SAH.