Inhaled nitric oxide: A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction

Abstract

Background. We examined the effects of inhalation of 5-80 ppm nitric oxide (NO) gas on the normal and acutely constricted pulmonary circulation in awake lambs. Methods and Results. Spontaneous breathing of nitric oxide (an endothelium-derived relaxing factor) at 40 ppm or more reversed acute pulmonary vasoconstriction within 3 minutes either because of infusion of the stable thromboxane endoperoxide analogue U46619 or because of pulmonary hypertension due to breathing a hypoxic gas mixture. Systemic vasodilation did not occur. Pulmonary vasodilation by NO inhalation was produced during infusion of U46619 for periods of 1 hour without observing evidence of short-term tolerance. Pulmonary hypertension resumed within 3-6 minutes of ceasing NO inhalation. In the normal lamb, the pulmonary vascular resistance, systemic vascular resistance, cardiac output, left atrial and central venous pressures were unaltered by NO inhalation. Conclusion. Breathing 80 ppm NO for 3 hours did not increase either methemoglobin or extravascular lung water levels or modify lung histology compared with those in control lambs.