Am. J. Respir. Crit. Care Med., Vol 150, No. 1, 07 1994, 227-232.
Mucosal nitric oxide may tonically suppress airways plasma exudation
JS Erjefalt, I Erjefalt, F Sundler and CG Persson
Department of Medical Cell Research, University of Lund, Sweden.
In a search for airway epithelial mechanisms that may affect the
subepithelial microcirculation, we examined plasma exudation responses to
NG-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 125I-albumin and/or colloidal gold
particles (5 nm) intravenously. Luminal entry of plasma was determined by
the levels of 125I-albumin in tracheal lavage fluid. Topical L-NAME (2.2,
9, and 22 mumol), but not intravenous L-NAME (375 mumol/kg), produced
plasma exudation into the airway lumen (p < 0.01 to p < 0.001). The
L-NAME enantiomer NG-nitro-D-arginine-methyl ester (D- NAME, 9 mumol)
produced no exudative response. Coadministration of L- arginine (27 mumol)
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 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.
