The effect of the nitric oxide synthase inhibitor N-γ-nitro- l-argine methyl ester on hypoxic pulmonary vasoconstriction

Abstract

We studied the role of nitric oxide in the regulation of pulmonary arterial tone and hypoxic pulmonary vasoconstriction. Rat pulmonary arteries ( n=65, diameter=440±12 μm) were loaded to 17.5 mm Hg in a wire myograph and incubated with the nitric oxide synthase inhibitor N-γ-nitro- l-argine methyl ester ( l-NAME; 1, 10 or 100 μM) or distilled water (50 μl) prior to preconstriction with either 100 μM prostaglandin F 2α followed by acetylcholine (0.1–100 μM) or 5 μM prostaglandin F 2α followed by hypoxia. Concentrations of l-NAME (10 and 100 μM) which attenuated acetylcholine dilatation, elevated basal tone from 0.2±0.5% to 9.4±2.1% ( P<0.01) and 18.3±3.2% ( P<0.001), respectively, potentiated contraction to 5 μM prostaglandin F 2α from 35.9±3.1% to 56.2±6.8% ( P<0.05) and 66.4±5.8% ( P<0.001), respectively, but had no significant effect on hypoxic pulmonary vasoconstriction. This suggests basal pulmonary nitric oxide release occurs, as well as in response to agonist-induced contraction, but not hypoxic pulmonary vasoconstriction.