MUCOSAL NITRIC-OXIDE MAY TONICALLY SUPPRESS AIRWAYS PLASMA EXUDATION

In a search for airway epithelial mechanisms that may affect the subepithelial microcirculation, we examined plasma exudation responses to N-G-nitro-L-arginine-methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor. L-NAME was applied topically on the tracheal mucosa of guinea pigs that had previously received I-125-albumin and/or colloidal gold particles (5 nm) intravenously. Luminal entry of plasma was determined by the levels of I-125-albumin in tracheal lavage fluid. Topical L-NAME (2.2, 9, and 22 mu mol), but not intravenous L-NAME (375 mu mol/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 extravasated plasma was distributed in the lamina propria and between epithelial cells (colloidal gold). The epithelial surface structure (scanning electron microscopy) appeared intact. Staining with nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase suggested that epithelial basal cells may contain nitric oxide synthases. We suggest that endogenously released nitric oxide from epithelial or other superficial cells tonically suppresses the macromolecular permeability of the subepithelial microcirculation.