A mechanism of nitric oxide-induced surfactant dysfunction. Hallman, Mikko, Kristina Bry, and Urpo Lappalainen. Division of Neonatal Medicine, Department of Pediatrics, University of California, Irvine, California 92717
APStracts 3:0082A, 1996.
Inhaled nitric oxide (NO) may modify surfactant either by interacting with the surfactant complex or by changing the capacity of the proteins of the epithelial lining fluid to inhibit the surface activity. Natural surfactant was exposed to NO (80 ppm) in air in vitro while the gas-liquid surface was cycled. In the presence or absence of oxidants (Fe++, xanthine, xanthine oxidase), surfactant exposed to NO retained the high surface activity significantly better than control surfactants exposed to air. Two surfactant inhibitors, hemoglobin (Hb) and albumin, were separately exposed to NO. In contrast to albumin, NO-exposed Hb and methemoglobin (16 to 125 [mu]g/ml) decreased the surface activity at low surfactant concentrations, whereas native Hb had no effect. Surfactant recovered by sedimentation after exposure to methemoglobin had decreased surface activity, and contained methemoglobin, whereas Hb did not bind to surfactant. Acidic phospholipid phosphatidylglycerol increased the binding of methemoglobin to surfactant. The methemoglobin-induced decrease in surface activity was elicited in the presence of surfactant proteins, including a peptide mimicking surfactant protein B. Methemoglobin (but not Hb) added to a low dose of exogenous surfactant decreased the efficacy of surfactant to improve the lung compliance of premature rabbits. We propose that inhaled NO promotes the surface activity of surfactant during tidal ventilation and that in high permeability lung edema and surfactant deficiency, inhaled NO increases the inhibition of surface activity by converting Hb to methemoglobin in the alveolar space. 

Received 11 April 1995; accepted in final form 17 January 1996.
APS Manuscript Number A398-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96