A mechanism of nitric oxide-induced surfactant dysfunction.
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 parts/million) in air in vitro while the gas-liquid surface was cycled. In the presence or absence of oxidants (Fe2+, 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 (MetHb; 16-125 micrograms/ml) decreased the surface activity at low surfactant concentrations, whereas native Hb had no effect. Surfactant recovered by sedimentation after exposure to MetHb had decreased surface activity and contained MetHb, whereas Hb did not bind to surfactant. Acidic phospholipid phosphatidylglycerol increased the binding of MetHb to surfactant. The MetHb-induced decrease in surface activity was elicited in the presence of surfactant proteins, including a peptide mimicking surfactant protein B. MetHb (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 MetHb in the alveolar space.
Hallman
M
M
Department of Pediatrics, University of California, Irvine 92717, USA.
Bry
K
K
Lappalainen
U
U
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006454:Hemoglobins / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects*; D008176:Lung Volume Measurements; D009569:Nitric Oxide / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000494:pharmacology; D011312:Pressure; D011817:Rabbits; D013501:Surface-Active Agents
D006454:Hemoglobins; D010713:Phosphatidylcholines; D013501:Surface-Active Agents; D009569:Nitric Oxide