Neonatal dexamethasone treatment increases the risk for pulmonary hypertension in adult rats

Dexamethasone (Dex) treatment during a critical period of lung development causes lung hypoplasia in infant rats. However, the effects of Dex on the p ulmonary circulation are unknown. To determine whether Dex increases the ri sk for development of pulmonary hypertension, we treated newborn Sprague-Da wley rats with Dex (0.25 mu g/day, days 3-13). Litters were divided equally between Dex-treated and vehicle control (ethanol) rats. Rats were raised i n either room air until 10 wk of age (normoxic groups) or room air until 7 wk of age and then in a hypoxia chamber (inspired O-2 fraction = 0.10; hypo xic groups) for 3 wk to induce pulmonary hypertension. Compared with vehicl e control rats, Dex treatment of neonatal rats reduced alveolarization (by 42%; P < 0.05) and barium-filled pulmonary artery counts (by 37%; P < 0.05) in 10-wk-old adults. Pulmonary arterial pressure and the ratio of right ve ntricle to left ventricle plus septum weights (RV/LV+S) were higher in 10-w k-old Dex-treated normoxic rats compared with those in normoxic control rat s (by 16 and 16% respectively; P < 0.05). Small pulmonary arteries of adult normoxic Dex-treated rats showed increased vessel wall thickness compared with that in control rats (by 15%; P < 0.05). After 3 wk of hypoxia, RV/LVS values were 36% higher in rats treated with Dex in the neonatal period co mpared with those in hypoxic control rats (P < 0.05). RV/LV+S was 42% highe r in hypoxic control rats compared with those in normoxic control rats (P < 0.05). We conclude that Dex treatment of neonatal rats caused sustained lu ng hypoplasia and increased pulmonary arterial pressures and augmented the severity of hypoxia-induced pulmonary hypertension in adult rats.