NITRIC-OXIDE ACCOUNTS FOR HISTAMINE-INDUCED INCREASES IN MACROMOLECULAR EXTRAVASATION

The goal of this study was to determine the role of nitric oxide in hi stamine-induced increases in macromolecular extravasation in the hamst er cheek pouch in vivo. We used intravital fluorescent microscopy and fluorescein isothiocyanate dextran (FITC-dextran; mol wt = 70,000 K) t o examine extravasation from postcapillary venules in response to hist amine before and after application of an enzymatic inhibitor of nitric oxide, NG-monomethyl-L-arginine (L-NMMA; 1.0 CLM) Increases in extrav asation of macromolecules were quantitated counting the number of venu lar leaky sites. Histamine (1.0 and 5.0 CLM) increased the number of v enular leaky sites from zero (basal conditions) to 11 +/- 1 and 21 +/- 2/0.11 cm(2), respectively. Superfusion of L-NMMA (1.0 mu M) and LY-8 3583 (1.0 mu M) significantly decreased histamine-induced formation of venular leaky sites, whereas L-arginine (100 mu M) potentiated histam ine-induced formation of venular leaky sites. In contrast, superfusion of N-G-monomethyl-D-arginine (1.0 mu M) 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 subseq uent activation of guanylate cyclase, plays an important role in macro molecular efflux in vivo in response to histamine.