Estradiol-induced attenuation of pulmonary hypertension is not associated with altered eNOS expression

Female rats develop less severe pulmonary hypertension (PH) in response to chronic hypoxia compared with males, thus implicating a potential role for ovarian hormones in mediating this gender difference. Considering that estr ogen upregulates endothelial nitric oxide (NO) synthase (eNOS) in systemic vascular tissue, we hypothesized that estrogen inhibits hypoxic PH by incre asing eNOS expression and activity. To test this hypothesis, we examined re sponses to the endothelium-derived NO-dependent dilator ionomycin and the N O donors S-nitroso-N-acetylpenicillamine and spermine NONOate in U-46619-co nstricted, isolated, saline-perfused lungs from the following groups: 1) no rmoxic rats with intact ovaries, 2) chronic hypoxic (CH) rats with intact o varies, 3) CH ovariectomized rats given 17 beta -estradiol (E(2)beta), and 4) CH ovariectomized rats given vehicle. Additional experiments assessed pu lmonary eNOS levels in each group by Western blotting. Our findings indicat e that E(2)beta attenuated chronic hypoxia-induced right ventricular hypert rophy, pulmonary arterial remodeling, and polycythemia. Furthermore, althou gh CH augmented vasodilatory responsiveness to ionomycin and increased pulm onary eNOS expression, these responses were not potentiated by E(2)beta. Fi nally, responses to S-nitroso-N-acetylpenicillamine and spermine NONOate we re similarly attenuated in all CH groups compared with normoxic control gro ups. We conclude that the inhibitory influence of E(2)beta on chronic hypox ia-induced PH is not associated with increased eNOS expression or activity.