Continuous inhalation of nitric oxide protects against development of pulmonary hypertension in chronically hypoxic rats.
Exposure to hypoxia and subsequent development of pulmonary hypertension is associated with an impairment of the nitric oxide (NO) mediated response to endothelium-dependent vasodilators. Inhaled NO may reach resistive pulmonary vessels through an abluminal route. The aim of this study was to investigate if continuous inhalation of NO would attenuate the development of pulmonary hypertension in rats exposed to chronic hypoxia. In conscious rats previously exposed to 10% O2 for 3 wk, short-term inhalation of NO caused a dose-dependent decrease in pulmonary artery pressure (PAP) from 44 +/- 1 to 32 +/- 1 mmHg at 40 ppm with no changes in systemic arterial pressure, cardiac output, or heart rate. In normoxic rats, acute NO inhalation did not cause changes in PAP. In rats simultaneously exposed to 10% O2 and 10 ppm NO during 2 wk, right ventricular hypertrophy was less severe (P < 0.01), and the degree of muscularization of pulmonary vessels at both alveolar duct and alveolar wall levels was lower (P < 0.01) than in rats exposed to hypoxia 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 demonstrate that prolonged inhalation of low concentrations of NO induces sustained pulmonary vasodilation and reduces pulmonary vascular remodeling in response to chronic hypoxia.
Département de Physiologie, INSERM U 296, Hôpital Henri Mondor, Créteil, France.
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C
Kouyoumdjian
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S
Adnot
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M
Levame
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S
Eddahibi
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H
Bousbaa
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B
Raffestin
D000280:Administration, Inhalation; D000818:Animals; D002908:Chronic Disease; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000517:prevention & control*; D000860:Hypoxia / Q000150:complications*; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D009569:Nitric Oxide