Protection by Estradiol 17β Against the Development of Hypoxic Pulmonary Hypertension in Male Rats

We evaluated the effect of estradiol 17β treatment on the development of pulmonary hypertension and vascular remodeling in male rats exposed to chronic hypoxia. Rats were treated with either placebo or estradiol 17β slow release pellets and exposed to either normoxic air or 10% oxygen for 10 days. Hypoxia elevated right ventricular pressure (RVP) from 19.0 ± 1.5 mm Hg in placebo normoxic to 34.4 ± 1.6 mm Hg in hypoxic animals (p < 0.01). Hypoxia also increased the right ventricle to left ventricle + septum weight ratio (RV/LV + S) (from 0.29 ± 0.01 to 0.44 ± 0.01; p < 0.01) and increased medial thickening in distal pulmonary vessels (from 7.4 ± 1.1% to 14.9 ± 1.4%; p < 0.01). Estradiol treatment blunted the rise in RVP (23.3 ± 2.4 mm Hg; p < 0.01), the RV/LV + S ratio (0.28 ± 0.05; p < 0.01), and vascular medial thickening (9.2 ± 0.8%; p < 0.05) in hypoxic animals, but did not significantly affect these parameters in normoxic rats. Estradiol produced a comparable decrease in hematocrit in both normoxic and hypoxic animals (p < 0.05). We conclude that estradiol 17β may protect against the development of hypoxic pulmonary hypertension and vascular remodeling in male rats exposed to chronic hypoxia. The exact mechanism of this protection remains unclear.