DUAL INHIBITION OF ANGIOTENSIN II RECEPTOR- NEPRILYSIN COULD POSTPONE THE OXIDATIVE STRESS AND FIBROSIS IN THE GENITALTRACT OF FEMALE SPONTANEOUS HYPERTENSIVE RATS

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Objective: Hypertension-mediated organ damage(HMOD) usually refers to the heart, brain, kidney and peripheral blood vessels. Our previous study proved that female hypertensive patients are more likely to develop sexual dysfunction than women with normal blood pressure, female genital tract can also be described as one of the HMOD. In this study, we investigated the effects of AT1 receptor and neprilysin double blocker (Sacubitril / valsartan) on oxidative stress and fibrosis in the genital tract of female spontaneously hypertensive rats (SHR) rats. Design and method: 16-week-old SPF-grade SHR rats were randomly divided into sacubitril / valsartan group, valsartan group, diuretic group (chlorothiazone),SHR group, and WKY group with 10 rats in each group. The systolic blood pressure(SBP), diastolic blood pressure(DBP) and mean arterial blood pressure(MBP) were obtained by measuring rat tail artery pressure. After 12 weeks, all the rats were operated, and their vaginal tissues were taken. The oxidative stress index (eNOS, nNOS protein expression) was measured by Western blotting, and the degree of vaginal fibrosis was observed by HE staining and Masson staining. Results: Sacubitril/valsartan, valsartan and chlorothiazone could all significantly reduce blood pressure, including SBP, DBP and MBP in SHR rats, and compared with valsartan and chlorothiazone groups, the decrease of SBP insacubitril / valsartan group was more significant.(p < 0.01). Compared with WKY group, the relative expression of eNOS, nNOS protein in vaginal tissue of SHR group was significantly lower than that of the control group, and there was significant difference between two groups (P < 0.01). In SHR, the relative expression of eNOS, nNOS protein in sacubitril / valsartan group and valsartan group was significantly up-regulated (P < 0.01). In SHR group, the thickness of vaginal epithelium was significantly increased, the collagen fibers increased significantly, and arranged disorder. The small artery wall in vaginal was thickened and stenoses. Conclusions: The gentital tract fibrosis in female SHR rats are related to oxidative stress. Sacubitril / valsartan is able to inhibit oxidative stress and inflammation, to reduce the fibrosis, and thus ameliorate the gentital tract remodeling in female SHR rats.