MUCOSAL NITRIC-OXIDE MAY TONICALLY SUPPRESS AIRWAYS PLASMA EXUDATION

In a search for airway epithelial mechanisms that may affect the subep ithelial microcirculation, we examined plasma exudation responses to N -G-nitro-L-arginine-methyl ester (L-NAME), a nitric oxide synthase (NO S) inhibitor. L-NAME was applied topically on the tracheal mucosa of g uinea pigs that had previously received I-125-albumin and/or colloidal gold particles (5 nm) intravenously. Luminal entry of plasma was dete rmined by the levels of I-125-albumin in tracheal lavage fluid. Topica l L-NAME (2.2, 9, and 22 mu mol), but not intravenous L-NAME (375 mu m ol/kg), produced plasma exudation into the airway lumen (p < 0.01 to p < 0.001). The L-NAME enantiomer N-G-nitro-D-arginine-methyl ester (D- NAME, 9 mu mol) produced no exudative response. Coadministration of L- arginine (27 mu mol) abolished the L-NAME-induced exudation. The extra vasated plasma was distributed in the lamina propria and between epith elial cells (colloidal gold). The epithelial surface structure (scanni ng electron microscopy) appeared intact. Staining with nicotinamide ad enine dinucleotide phosphate (NADPH)-diaphorase suggested that epithel ial basal cells may contain nitric oxide synthases. We suggest that en dogenously released nitric oxide from epithelial or other superficial cells tonically suppresses the macromolecular permeability of the sube pithelial microcirculation.