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The role of estrogen receptors in the RVLM of renovascular hypertensive rats

      It is well stablished that 17β-estradiol (E2) is a cardiovascular protector in part via reduction of sympathetic vasomotor activity. However, there is no information regarding the estrogen receptors (ESR1and GPER) actions in the rostroventrolateral medulla (RVLM) in the 2kidney-1clip (2 K-1C) hypertension model. Thus, we investigate the role of estrogen receptors within the RVLM on sympathetic activity in 2 K-1C male Wistar rats. Protein expression of ESR1 and GPER within the RVLM were avaluated throught Western blot assay. Bilateral microinjection of E2 (ESR1 and GPER agonist), G1 (GPER agonist) and ICI182,780 (ESR1 antagonist) microinjections into the RVLM were performed in control (C) and 2K1C rats, six weeks after renal clipping. Renal sympathetic nerve activity (rSNA) and mean arterial blood pressure (MAP) were recorded in urethane anesthetized rats. A significant increase in ESR1(2K1C 300%n = 7) and GPER (2K1C 800%n = 8) expression was found in 2 K-1C rats. Losartan 2K1C treated significantly reduced GPER expression in the RVLM (300%n = 5). E2 microinjection decreased MAP(C,Δ-23.5 ± 2.3n = 6; and 2K1CΔ-16.6 ± 1.5 mmHg n = 6) and rSNA (C,Δ-40.8 ± 8n = 6 and 2K1CΔ-19.1 ± 2.3ppsn = 6) the response was significantly reduced in the 2K1C. However, GI into the RVLM induced larger MAP increase (C,Δ 22 ± 6.6 n = 5 and 2K1C,Δ41.83 ± 4.4 mmHg n = 6) and rSNA (C,Δ41 ± 6.4 n = 5 and H,Δ 65.8 ± 8.5pps n = 5), in 2K1C. No difference was found, however, in reponse to ICI microinjection between groups. E2 apparently has opposed functions into the RVLM depending on which receptor (ESR1 or GPER) is predominantly active in 2 K-1C. This imbalance seems to contribute for the sympathoexcitation and MAP in renovascular hypertension. Supported by: FAPESP, CAPES and CNPq
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