Dose-response relationship for inhaled nitric oxide in experimental pulmonary hypertension in sheep

We have examined the effect of inhaled nitric oxide 4-512 p.p.m. in six sheep with pulmonary hypertension induced first with hypoxia and then with 6 micrograms kg-1 of E. coli endotoxin. A similar dose-dependent reduction in pulmonary artery pressure occurred in pulmonary hypertension induced by hypoxia or endotoxin, with a maximum effect of 25-30% decrease with nitric oxide 64 p.p.m. Increasing the dose to 512 p.p.m. had no further effect. The ED50 for inhaled nitric oxide was 39 p.p.m. for pulmonary hypertension induced by hypoxia and 48 p.p.m. for endotoxin-induced pulmonary hypertension. A dose-dependent increase in arterial oxygenation, which reached a maximum with nitric oxide 64 p.p.m., was seen with inhaled nitric oxide after endotoxin infusion. If the toxicity of inhaled nitric oxide can be determined, it may prove useful in the treatment of pulmonary hypertension secondary to the adult respiratory distress syndrome.