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  • Title: Angiotensin AT1 receptors in paraventricular nucleus contribute to sympathetic activation and enhanced cardiac sympathetic afferent reflex in renovascular hypertensive rats.
    Author: Chen AD, Zhang SJ, Yuan N, Xu Y, De W, Gao XY, Zhu GQ.
    Journal: Exp Physiol; 2011 Feb; 96(2):94-103. PubMed ID: 21097645.
    Abstract:
    Sympathetic activity is enhanced in hypertension, which contributes to the pathogenesis of hypertension and progression of organ damage. The cardiac sympathetic afferent reflex (CSAR) is enhanced in renovascular hypertension and involved in the sympathetic activation. The present study was designed to investigate whether angiotensin II (Ang II) and Ang II type 1 (AT(1)) receptors in paraventricular nucleus (PVN) contribute to the enhanced CSAR and sympathetic outflow in experimental renovascular hypertensive rats. Hypertension was induced by the two-kidney one-clip (2K1C) method. The normotensive rats underwent sham operation (Sham). Acute experimentation was carried out at the end of the 4th week. Under urethane and α-chloralose anaesthesia, the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in rats with sino-aortic denervation and cervical vagotomy. The AT(1) receptor expression was determined with Western blot. The CSAR was evaluated by the response of RSNA and MAP to epicardial application of 1.0 nmol of capsaicin. The AT(1) receptor expression in the PVN was increased, and Ang II in the PVN augmented the enhanced CSAR and RSNA in 2K1C rats. The effects of Ang II were abolished by pretreatment with the AT(1) receptor antagonist, losartan, in 2K1C rats. Losartan in the PVN normalized the enhanced CSAR and decreased the RSNA and MAP in 2K1C rats. These results indicate that the increased activity of AT(1) receptors in the PVN contributes to the enhanced CSAR and excessive sympathetic activation in renovascular hypertensive rats.
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