CONTINUOUS INHALATION OF NITRIC-OXIDE PROTECTS AGAINST DEVELOPMENT OFPULMONARY-HYPERTENSION IN CHRONICALLY HYPOXIC RATS

Exposure to hypoxia and subsequent development of pulmonary hypertensi on is associated with an impairment of the nitric oxide (NO) mediated response to endothelium-dependent vasodilators. Inhaled NO may reach r esistive pulmonary vessels through an abluminal route. The aim of this study was to investigate if continuous inhalation of NO would attenua te the development of pulmonary hypertension in rats exposed to chroni c hypoxia. In conscious rats previously exposed to 10% O-2 for 3 wk, s hort-term inhalation of NO caused a dose-dependent decrease in pulmona ry artery pressure (PAP) from 43 +/- 1 to 32 +/- 1 mmHg at 40 ppm with no changes in systemic arterial pressure, cardiac output, or heart ra te. In normoxic rats, acute NO inhalation did not cause changes in PAP . In rats simultaneously exposed to 10% O-2 and 10 ppm NO during 2 wk, right ventricular hypertrophy was less severe (P < 0.01), and the deg ree of muscularization of pulmonary vessels at both alveolar duct and alveolar wall levels was lower (P < 0.01) than in rats exposed to hypo xia alone. Tolerance to the pulmonary vasodilator effect of NO did not develop after prolonged inhalation. Brief discontinuation of NO after 2 wk of hypoxia plus NO caused a rapid increase in PAP. These data de monstrate that prolonged inhalation of low concentrations of NO induce s sustained pulmonary vasodilation and reduces pulmonary vascular remo deling in response to chronic hypoxia.