title: Role of nitric oxide in histamine-induced increases in permeability of the blood-brain barrier.
abstract: While previous studies have examined the effects of histamine on the permeability of the blood-brain barrier and reactivity of cerebral blood vessels, cellular mechanisms which account for histamine-induced affects on the cerebral microcirculation are not clear. The goals of this study were to determine the role of nitric oxide in histamine-induced increases in permeability of the blood-brain barrier and dilatation of pial arterioles. We examined the pial microcirculation in rats using intravital fluorescence microscopy. Permeability of the blood-brain barrier (clearance of fluorescent-labeled dextran; molecular weight 10,000 daltons; FITC-dextran-10K) and diameter of pial arterioles were measured in the absence and presence of histamine (10 and 100 microM). During superfusion with vehicle (saline), clearance of FITC-dextran-10K from pial vessels was minimal and diameter of pial arterioles remained constant. Topical application of histamine (10 and 100 microM) produced an increase in clearance of FITC-dextran-10K and diameter of pial arterioles. To determine a potential role for nitric oxide in histamine-induced increases in permeability of the blood-brain barrier and dilatation of pial arterioles, we examined the effects of NG-monomethyl-L-arginine (L-NMMA; 10 microM). L-NMMA inhibited histamine-induced increases in permeability of the blood-brain barrier and attenuated histamine-induced dilatation of cerebral arterioles. The findings of the present study suggest that histamine increases permeability of the blood-brain barrier and diameter of pial arterioles via the synthesis/release of nitric oxide or a nitric oxide containing compound.
authors.affiliation: Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Mayhan
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D004353:Drug Evaluation, Preclinical; D006632:Histamine / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D008970:Molecular Weight; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D011920:Rats, Inbred WF; D014665:Vasodilator Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D006633:Histamine Antagonists; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D006632:Histamine; D000241:Adenosine