Nitric oxide accounts for histamine-induced increases in macromolecular extravasation.
The goal of this study was to determine the role of nitric oxide in histamine-induced increases in macromolecular extravasation in the hamster cheek pouch in vivo. We used intravital fluorescent microscopy and fluorescein isothiocyanate dextran (FITC-dextran; mol wt = 70,000 K) to examine extravasation from postcapillary venules in response to histamine before and after application of an enzymatic inhibitor of nitric oxide, NG-monomethyl-L-arginine (L-NMMA; 1.0 microM). Increases in extravasation of macromolecules were quantitated counting the number of venular leaky sites. Histamine (1.0 and 5.0 microM) increased the number of venular leaky sites from zero (basal conditions) to 11 +/- 1 and 21 +/- 2/0.11 cm2, respectively. Superfusion of L-NMMA (1.0 microM) and LY-83583 (1.0 microM) significantly decreased histamine-induced formation of venular leaky sites, whereas L-arginine (100 microM) potentiated histamine-induced formation of venular leaky sites. In contrast, superfusion of NG-monomethyl-D-arginine (1.0 microM) did not inhibit the formation of venular leaky sites in response to histamine. Thus the findings of the present study suggest that production of nitric oxide, and subsequent activation of guanylate cyclase, plays an important role in macromolecular efflux in vivo in response to histamine.
Mayhan
W G
WG
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198-4575.
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D004357:Drug Synergism; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D046911:Macromolecular Substances; D008297:Male; D008647:Mesocricetus; D009569:Nitric Oxide / Q000502:physiology*; D014699:Venules / Q000378:metabolism; D019323:omega-N-Methylarginine
D000634:Aminoquinolines; D046911:Macromolecular Substances; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D006632:Histamine; C041715:6-anilino-5,8-quinolinedione; D001120:Arginine; D006162:Guanylate Cyclase