Higher endogenous estrogen levels in female and pregnant rats significantly attenuated hypoxia-induced elevations in right ventricular systolic pressure and pulmonary arterial remodeling compared to male and ovariectomized rats.
Does endogenous estrogen attenuate hypoxia-induced pulmonary hypertension in rat models?
Endogenous estrogen attenuates hypoxia-induced pulmonary hypertension in rats by inhibiting pulmonary arterial vasoconstriction and smooth muscle cell proliferation.
p-value: p=<0.05
Exogenous estrogen was shown to exert various beneficial effects on multiple diseases including hypoxia-induced pulmonary hypertension (HPH). However, the effect of endogenous estrogen on HPH was seldom investigated. In the present study, we explored the protective effects and mechanisms of endogenous estrogen on hypoxia-induced pulmonary hypertension. Male, female, pregnant and ovariectomized rats were housed in a hypoxic condition for 21 days, and then hemodynamic together with morphologic indexes of pulmonary circulation were measured. The right ventricular systolic pressure, mean pulmonary artery pressure, right ventricular hypertrophy index, and arterial remodeling index were significantly elevated after chronic hypoxia exposure. Experimental data showed less severity in female, especially in pregnant rats. In vitro, artery rings of different sex or estrus cycle rats were obtained, and then artery rings experiments were performed to investigate pulmonary vasoconstriction by recording the maximum phase II vasoconstriction. Data showed that the vasoconstriction was milder in proestrus female than diestrus female or male groups, which could be leveled by treating U0126 (a MAPK pathway inhibitor). Pulmonary arterial smooth muscle cells isolated from different sex or estrus cycle rats were cultured in the condition of 2% oxygen for 24 hours, and cell proliferation was evaluated by the 3H-thymidine incorporation assay. Cells from proestrus rats exhibited lower proliferation than the other groups, which could be countered by both U0126 and raloxifene (a selective estrogen receptor modulator). Serum estradiol levels were detected, and rats with higher levels showed less severity of pulmonary hypertension. Conclusively, endogenous estrogen may alleviate hypoxia-induced pulmonary hypertension by attenuating vasoconstriction through non-genomic mechanisms and inhibiting smooth muscle cells proliferation through both genomic and non-genomic mechanisms.
Xu et al. (2013) studied Hypoxia-induced pulmonary hypertension (n=40). Endogenous estrogen vs. Low endogenous estrogen (male or ovariectomized rats) was evaluated on Right ventricular systolic pressure (RVSP) and pulmonary vascular remodeling (p=<0.05). Higher endogenous estrogen levels in female and pregnant rats significantly attenuated hypoxia-induced elevations in right ventricular systolic pressure and pulmonary arterial remodeling compared to male and ovariectomized rats.