HYPOXIA FAILS TO CAUSE HYPERTROPHY OR HYPERPI.ASIA OF FETAL PULMONARY ARTERY SMOOTH MUSCLE CELLS IN VITRO

Abstract

Persistent pulmonary hypertension of the newborn (PPHN) is associated with both prenatal hypoxia and increased pulmonary arterial (PA) smooth muscle mass in both clinical (Gersony, J Pediatr 82:1103, 1973; Murphy et al, J Pediatr 98:962, 1981) and experimental (Goldberg et al, Pediatrics 48:528, 1971; Gersony et al, J Pediatr 89:631, 1976) circumstances. To assess the ability of hypoxia to directly produce increased PA smooth muscle cell (SMC) mass, we examined the effect of hypoxia on the proliferation and size of SMC cultured from fetal bovine pulmonary arteries. SMC were cultured under ambient oxygen tensions (pO₂) ranging from 2 to 145 torr. Both the rate of cell proliferation and the final cell density (10 days of culture) were decreased in cultures incubated at pO₂ less than 55 torr. Final cell densities at pO₂ of 2 or 24 torr were only 18% and 80%, respectively, of that seen at pO₂ of 85 to 145 torr (p<0.002). Oxygen tension did not affect SMC size, as the protein:DNA ratio was constant. Therefore, hypoxia does not produce either proliferation or hypertrophy of PA SMC in vitro. We conclude that prenatal hypoxia does not act directly on SMC in the PA to produce the increased PA SMC mass observed in infants with PPHN. Other mediators of this developmental abnormality must be sought. (Supported by NIH Grant HD06763 and a Medical Student Traineeship of the Cystic Fibrosis Foundation.)

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