AHEART February 47/2

Ooi, Henry, Elaine Cadogan, Michèle Sweeney, Katherine Howell, R. G. O’Regan, and Paul McLoughlin. Chronic hypercapnia inhibits hypoxic pulmonary vascular remodeling. Am. J. Physiol. Heart Circ. Physiol. 278: H331–H338, 2000.—Chronic hypercapnia is commonly found in patients with severe hypoxic lung disease and is associated with a greater elevation of pulmonary arterial pressure than that due to hypoxia alone. We hypothesized that hypercapnia worsens hypoxic pulmonary hypertension by augmenting pulmonary vascular remodeling and hypoxic pulmonary vasoconstriction (HPV). Rats were exposed to chronic hypoxia [inspiratory O2 fraction (FIO2) 5 0.10], chronic hypercapnia (inspiratory CO2 fraction 5 0.10), hypoxia-hypercapnia (FIO2 5 0.10, inspiratory CO2 fraction 5 0.10), or room air. After 1 and 3 wk of exposure, muscularization of resistance blood vessels and hypoxia-induced hematocrit elevation were significantly inhibited in hypoxia-hypercapnia compared with hypoxia alone (P , 0.001, ANOVA). Right ventricular hypertrophy was reduced in hypoxia-hypercapnia compared with hypoxia at 3 wk (P , 0.001, ANOVA). In isolated, ventilated, blood-perfused lungs, basal pulmonary arterial pressure after 1 wk of exposure to hypoxia (20.1 6 1.8 mmHg) was significantly (P , 0.01, ANOVA) elevated compared with control conditions (12.1 6 0.1 mmHg) but was not altered in hypoxia-hypercapnia (13.5 6 0.9 mmHg) or hypercapnia (11.8 6 1.3 mmHg). HPV (FIO2 5 0.03) was attenuated in hypoxia, hypoxia-hypercapnia, and hypercapnia compared with control (P , 0.05, ANOVA). Addition of Nv-nitro-Larginine methyl ester (1024 M), which augmented HPV in control, hypoxia, and hypercapnia, significantly reduced HPV in hypoxia-hypercapnia. Chronic hypoxia caused impaired endothelium-dependent relaxation in isolated pulmonary arteries, but coexistent hypercapnia partially protected against this effect. These findings suggest that coexistent hypercapnia inhibits hypoxia-induced pulmonary vascular remodeling and right ventricular hypertrophy, reduces HPV, and protects against hypoxia-induced impairment of endothelial function.