ROLE OF NITRIC-OXIDE IN DISRUPTION OF THE BLOOD-BRAIN-BARRIER DURING ACUTE HYPERTENSION

The goal of this study was to determine the role of nitric oxide in di sruption of the blood-brain barrier during acute hypertension. We exam ined the microcirculation of the cerebrum in vivo. Permeability of the blood-brain barrier was quantitated by the formation of venular leaky sites and clearance of fluorescent-labeled albumin (FITC-albumin) bef ore and during phenylephrine-induced acute hypertension. We compared d isruption of the blood-brain barrier during acute hypertension in untr eated rats and in rats treated for 1 h with topical application of N-G -monomethyl-L-arginine (L-NMMA; 100 mu M) or N-G-nitro-L-arginine meth yl ester (L-NAME; 100 mu M). Under control conditions, no venular leak y sites were visible and clearance of FITC-albumin was minimal in untr eated rats and in rats treated with topical application of nitric oxid e synthase inhibitors. Phenylephrine (20 mu g/kg/min for 5 min) infusi on increased systemic arterial pressure by a similar magnitude in all groups of rats and produced disruption of the blood-brain barrier in v enules. However, the magnitude of disruption of the blood-brain barrie r during acute hypertension was significantly less in rats treated wit h L-NMMA (52% reduction in the clearance of FITC-albumin) and L-NAME ( 47% reduction in clearance of FITC-albumin). The findings of the prese nt study suggest that synthesis/release of nitric oxide contributes to disruption of the blood-brain barrier during acute hypertension.