BACKGROUND: Nitric Oxide (NO) has been discovered to be an important endothelium-derived relaxing factor. The exogenous inhaled NO may diffuse from the alveoli to pulmonary vascular smooth muscle and produce pulmonary vasodilation, but any NO that diffuses into blood will be inactivated before it can produce systemic effects. To examine the effects of NO on pulmonary and systemic hemodynamics, NO was inhaled by experimental dogs in an attempt to reduce the increase in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) induced by hypoxia in dogs. METHODS: Eight mongrel dogs were studied while inhaling 1)50% O2 (baseline), 2)12% O2 in N2 (hypoxia), 3)followed by the same hypoxic gas mixture of O2 and N2 containing 20, 40 and 80 ppm of NO, respectively. RESULTS: Breathing at FIO2 0.12 nearly doubled the pulmonary vascular resistance from 173 56dyn sec cm-5 to 407 139dyn sec cm-5 and significantly increased the mean pulmonary artery pressure from 16 3mmHg to 22 4mmHg. After adding 20~80 ppm NO to the inspired gas while maintaining the FIO2 at 0.12, the mean pulmonary artery pressure decreased (p<0.05) to the level when breathing oxygen at FIO2 0.5 while the PaO2 and PaCO2 were unchanged. The pulmonary vascular resistance decreased significantly and the right ventricular stroke work index returned to a level similar to breathing at FIO2 0.5 by addition of NO into the breathing circuit. Pulmonary hypertension resumed within 3~5 minutes of ceasing NO inhalation. In none of our studies did inhaling NO produce systemic hypotension and elevate methemoglobin levels. CONCLUSIONS: Inhalation of 20~80 ppm NO selectively induced pulmonary vasodilation and reversed hypoxic pulmonary vasoconstriction without causing systemic vasodilation and bronchodilation. Methemoglobin and NO2 were within normal limit during the study.