Inhibition of nitric oxide synthase does not alter basal permeability of the blood-brain barrier.

The goal of the present study was to determine the role of basal synthesis/release of nitric oxide on the basal permeability characteristics of the blood-brain barrier to various sized molecules in vivo. We examined the pial microcirculation in rats using intravital fluorescence microscopy. Permeability of the blood-brain barrier was quantitated by calculating the clearance of fluorescent-labeled albumin (mol.wt.=69,000 Da; FITC-albumin), fluorescent-labeled dextran (mol.wt.=10,000 Da; FITC-dextran-10K) or sodium fluorescein (mol.wt.=376; NaFl) in the absence and presence of an inhibitor of nitric oxide synthase (N(G)-monomethyl-L-arginine; L-NMMA; 10 and 100 microM). During superfusion with vehicle, clearance of FITC-albumin, FITC-dextran-10K and NaFl from pial vessels and diameter of pial arterioles remained constant. To determine whether basal synthesis/release of nitric oxide affected basal permeability of the blood-brain barrier, we examined the effects of L-NMMA (10 and 100 microM). In addition, we examined the adherence of leukocytes to cerebral venular endothelium using rhodamine 6G. Although topical application of L-NMMA produced constriction of pial arterioles, L-NMMA did not alter the permeability characteristics of the blood-brain barrier to FITC-albumin, FITC-dextran-10K or NaFl. Further, the adherence of leukocytes to the endothelium appeared to be similar while suffusing with vehicle and L-NMMA (100 microM). Thus, the findings of the present study suggest that while basal synthesis/release of nitric oxide may play an important role in regulation of basal tone of cerebral blood vessels, it does not appear that basal synthesis/release of nitric oxide plays an important role in maintaining the integrity of the blood-brain barrier to large or small molecules.