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 disruption of the blood-brain barrier during acute hypertension. We examined 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) before and during phenylephrine-induced acute hypertension. We compared disruption of the blood-brain barrier during acute hypertension in untreated rats and in rats treated for 1 h with topical application of NG-monomethyl-L-arginine (L-NMMA; 100 microM) or NG-nitro-L-arginine methyl ester (L-NAME; 100 microM). Under control conditions, no venular leaky sites were visible and clearance of FITC-albumin was minimal in untreated rats and in rats treated with topical application of nitric oxide synthase inhibitors. Phenylephrine (20 micrograms/kg/min for 5 min) infusion increased systemic arterial pressure by a similar magnitude in all groups of rats and produced disruption of the blood-brain barrier in venules. However, the magnitude of disruption of the blood-brain barrier during acute hypertension was significantly less in rats treated with L-NMMA (52% reduction in the clearance of FITC-albumin) and L-NAME (47% reduction in clearance of FITC-albumin). The findings of the present study suggest that synthesis/release of nitric oxide contributes to disruption of the blood-brain barrier during acute hypertension.
Mayhan
W G
WG
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575, USA.
D000208:Acute Disease; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000098:blood supply; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016650:Fluorescein-5-isothiocyanate / Q000493:pharmacokinetics; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008657:Metabolic Clearance Rate; D008833:Microcirculation / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010656:Phenylephrine; D051381:Rats; D019323:omega-N-Methylarginine
D004791:Enzyme Inhibitors; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D016650:Fluorescein-5-isothiocyanate; D019331:NG-Nitroarginine Methyl Ester