Opening of the blood-brain barrier during cortical superfusion with histamine.
Histamine may influence cerebral microcirculation from the intravascular and parenchymal side. The latter route can be simulated by cortical superfusion. The effect of cortical superfusion with histamine (10(-9)-10(-3) M) on blood-brain barrier (BBB) permeability was studied in the cat by measuring extravasation of the tracers Na(+)-fluorescein (MW 376) or fluorescein isothiocyanate (FITC) labelled dextran (MW 62,000 or 145,000) by intravital fluorescence microscopy. Histamine induced an opening of BBB resulting in extravasation of small and large molecular weight tracers with threshold concentrations of 10(-9), 10(-8) and 10(-6) M for Na(+)-fluorescein, FITC-dextran 62,000 and 145,000, respectively. Once tracer extravasation had started the degree of extravasation increased with increasing concentrations of histamine in the superfusion fluid. Similar to histamine the H2 agonist impromidine (3 x 10(-12)-3 x 10(-9) M) induced a concentration dependent extravasation of Na(+)-fluorescein. 2-Pyridylethylamine which is 3-4 times more selective for H1 than for H2 receptors also induced an extravasation of Na(+)-fluorescein. Cortical superfusion with mepyramine (10(-7) M) or cimetidine (10(-4) M), which block the H1 and H2 receptors, respectively, already induced significant extravasation of Na(+)-fluorescein by themselves. These compounds could thus not be used as competitive antagonists to block histamine-induced extravasation. However, our data are in accord with data obtained during intravascular and topical application of histamine and support the hypothesis that H2 receptors at the luminal and abluminal membrane of the endothelium mediate the opening of the BBB.(ABSTRACT TRUNCATED AT 250 WORDS)
Schilling
L
L
Department of Physiology, Ludwig-Maximilians University, Munich, FRG.
Wahl
M
M
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects; D002415:Cats; D002540:Cerebral Cortex; D002927:Cimetidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019793:Fluorescein; D005452:Fluoresceins; D006632:Histamine / Q000494:pharmacology*; D017446:Impromidine / Q000494:pharmacology; D009994:Osmolar Concentration; D010477:Perfusion; D010841:Pia Mater / Q000098:blood supply; D011968:Receptors, Histamine / Q000502:physiology; D014666:Vasomotor System / Q000187:drug effects
D005452:Fluoresceins; D011968:Receptors, Histamine; D002927:Cimetidine; D006632:Histamine; D017446:Impromidine; D019793:Fluorescein