Fig. 2.

ET-1 loss in SMC attenuates the pulmonary vascular response to hypoxia. A: representative right ventricular systolic pressure (RVSP) tracings from individual mice exposed to chronic hypoxia. B: RVSP of SM22α-ET-1^−/− mice exposed to chronic hypoxia demonstrates a significant reduction in RVSP compared with control mice. Control and SM22α-ET-1^−/− littermates were exposed to normoxic (21% O₂) or hypoxic (10% O₂) conditions for 3 wk (control, n = 7; SM22α-ET-1^−/−, n = 9). **P < 0.01, SM22α-ET-1^−/− vs. control. C: right ventricular hypertrophy as assessed by Fulton's index (ratio of right ventricular weight to left ventricular + septal weight) in hypoxic mice (control, n = 4; SM22α-ET-1^−/−, n = 5). D: representative Movat pentachrome-stained sections show a decrease in muscularization in peripheral PA from SM22α-ET-1^−/− mice (right) exposed to chronic hypoxia. Magnification ×400, scale bar = 25 μm. Quantification of peripheral PA muscularization is expressed as the medial thickness index of pulmonary arteries ≤100 μm in diameter. Graph represents the means ± SE; n = 6 per genotype with 10 fields assessed per mouse. **P < 0.01. E: representative histology of barium-injected lungs of control and SM22α-ET-1^−/− mice after chronic hypoxia. Magnification ×100, scale bar = 100 μm. Mean vessel density assessed on barium-injected lungs is significantly increased in the lungs of SM22α-ET-1^−/− mice. Graph represents the means ± SE of the number of barium-filled distal PA (≤50 μm in external diameter) per 100 alveoli. n = 4 per genotype with 6 fields assessed per mouse. **P < 0.01. F: chronic hypoxia increases serum ET-1 concentration levels in both control and SM22α-ET-1^−/− mice. §P < 0.05, §§P < 0.01, hypoxia vs. normoxia.