Severe cerebral blood flow reduction inhibits nitric oxide synthesis.

Abstract

The purpose of this study was to investigate the relationship between cerebral blood flow (CBF) and nitric oxide (NO) synthesis using a rat model of transient forebrain ischemia of varying severity. Forebrain ischemia was induced for 30 min by occlusion of the bilateral common carotid arteries without hemorrhagic hypotension. The production of NO end-products (nitrite and nitrate) was measured by in vivo microdialysis, and CBF by the hydrogen clearance technique. Ischemia induced NO synthesis, although the increase in the quantity of NO end-products was not remarkable during the ischemic period but became prominent after reperfusion. Such increases were abolished by Nomega-nitro-L-arginine methyl ester (L-NAME), although 7-nitroindazole (7-NI) appeared to have only slight effects. The production of NO end-products during ischemia increased when the CBF during ischemia was less than 60 mL/100 g/min. In animals in which the CBF during ischemia was higher than 22.7 mL/100 g/min, the production of NO end-products increased gradually after the induction of ischemia and reached a peak during the reperfusion period, whereas in other animals in which the CBF during ischemia fell below 22.7 mL/100 g/min, the NO end-products decreased during ischemia and increased transiently after reperfusion. These results suggest that the increase in NO end-products is NO synthase (NOS)-dependent and that most of the increase is derived from endothelial NOS. It is also suggested that NO synthesis during ischemia is closely related to CBF, and that severe CBF reduction may inhibit NO synthesis.