ROLE OF NITRIC-OXIDE IN LEUKOTRIENE C4-INDUCED INCREASES IN MICROVASCULAR TRANSPORT

The goal of this study was to determine the role of nitric oxide in al terations in macromolecular transport of the hamster cheek pouch in vi vo in response to leukotriene C4. We used intravital fluorescent micro scopy to examine the transport of macromolecules across the hamster ch eek pouch in response to leukotriene C4 before and after application o f an enzymatic inhibitor of nitric oxide, N(G)-monomethyl-L-arginine ( L-NMMA; 1.0 muM). Increases in transport of macromolecules across the hamster cheek pouch were quantitated by the formation of venular leaky sites and clearance of fluorescein isothiocyanate-dextran (FITC-dextr an; mol wt = 70 K). Leukotriene C4 (1.0 and 3.0 nM) produced an increa se in the number of venular leaky sites and clearance of FITC-dextran- 70 K. Superfusion of L-NMMA (1.0 muM) significantly decreased leukotri ene C4-induced increases in venular leaky sites and clearance of FITC- dextran-70K. In addition, superfusion of LY-83583 (10 muM) significant ly decreased leukotriene C4-induced increases in venular leaky sites. In contrast, superfusion of N(G)-monomethyl-D-arginine (D-NMMA; 1.0 mu M), indomethacin (10 mg/kg iv), or diphenhydramine hydrochloride; 15-2 0 mg/kg iv) did not significantly alter leukotriene C4-induced increas es in venular leaky sites. Thus these findings suggest that production of nitric oxide and subsequent activation of guanylate cyclase play a n important role in formation of venular leaky sites and clearance of FITC-dextran-70K in response to application of leukotriene C4.