Sex-dependent changes in the pulmonary vasoconstriction potential of newborn rats following short-term oxygen exposure.

BACKGROUND: Chronic exposure to supplemental oxygen (O(2)) induces lung damage and mortality in a sex-dependent manner. The effect of short-term hyperoxia on the newborn pulmonary vasculature is unknown but is, however, of clinical significance in the neonatal resuscitation context. We hypothesize that short-term hyperoxia has a sex-dependent effect on the pulmonary vasculature.

METHODS: Following 1-h 100% O(2) exposure, the pulmonary arteries and lung tissues of newborn rats were evaluated.

RESULTS: Superoxide dismutase 3 (SOD3) expression in female pups' lungs was increased as compared with that in the lungs of male pups. As compared with air-treated pups, the response of male pups to thromboxane was increased by O(2), whereas the opposite effect was documented in the vessels of female pups. The enhanced force of hyperoxia-exposed arteries of the male pups was suppressed with superoxide or peroxynitrite scavengers, and increased lung SOD activity and hydrogen peroxide content were seen in female, but not in male, rats. Hyperoxia induced an increase in lung tissue oxidative products and Rho-kinase (ROCK) activity in male, but not in female, pups.

CONCLUSION: A lower lung SOD content and failure to upregulate SOD activity facilitates peroxynitrite generation and ROCK activation in hyperoxia-exposed males, predisposing them to pulmonary vasoconstriction. These observations, if relevant to humans, may explain the increased mortality and higher incidence of pulmonary hypertension in male neonates.