Enhanced pulmonary production of
nitric oxide (NO) has been implicated in the pathogenesis of
hepatopulmonary syndrome (HPS). NO inhibition with
N(G)-nitro-L-arginine methyl ester (
L-NAME) in both animals and humans with HPS has improved arterial
hypoxemia. We assessed the role of enhanced NO production in the pathobiology of arterial deoxygenation in HPS and the potential therapeutic efficacy of selective pulmonary NO inhibition. We investigated the effects of nebulized
L-NAME (162.0 mg) at 30 and 120 minutes on all intrapulmonary and extrapulmonary factors governing pulmonary gas exchange in 10 patients with HPS (60 +/- 7 [SD] yr; alveolar-arterial
oxygen gradient, range 19-76 mm Hg; arterial
oxygen tension, range 37-89 mm Hg). Nebulized
L-NAME maximally decreased exhaled NO (by -55%; P < .001), mixed venous
nitrite/
nitrate (by -12%; P = .02), and cardiac output (by -11%; P = .002) while increased systemic vascular resistance (by 11%; P = .008) and pulmonary vascular resistance (by 25%; P = .03). In contrast, ventilation-perfusion mismatching, intrapulmonary shunt and, in turn, arterial deoxygenation remained unchanged. In conclusion, gas exchange disturbances in HPS may be related to pulmonary
vascular remodeling rather than to an ongoing
vasodilator effect of enhanced NO production.