Department of Physiology, Nanjing Medical University, Nanjing, China.
Exp Physiol. 2011 Feb;96(2):94-103. doi: 10.1113/expphysiol.2010.054353. Epub 2010 Nov 19.
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.
交感神经活动在高血压中增强,这有助于高血压的发病机制和器官损伤的进展。心脏交感传入反射(CSAR)在肾血管性高血压中增强,并参与交感神经激活。本研究旨在探讨室旁核(PVN)中的血管紧张素 II(Ang II)和血管紧张素 II 型 1(AT(1))受体是否有助于增强实验性肾血管性高血压大鼠的 CSAR 和交感神经输出。高血压通过双肾一夹(2K1C)方法诱导。正常血压大鼠接受假手术(Sham)。在第 4 周末进行急性实验。在氨基甲酸乙酯和α-氯醛麻醉下,在去窦弓神经和颈迷走神经切断的大鼠中记录肾交感神经活动(RSNA)和平均动脉压(MAP)。用 Western blot 测定 AT(1)受体表达。通过心外膜应用 1.0 nmol 辣椒素评估 CSAR,记录 RSNA 和 MAP 的反应。PVN 中的 AT(1)受体表达增加,Ang II 在 PVN 中增强了 2K1C 大鼠增强的 CSAR 和 RSNA。在 2K1C 大鼠中,用 AT(1)受体拮抗剂洛沙坦预处理可消除 Ang II 的作用。PVN 中的洛沙坦使 2K1C 大鼠增强的 CSAR 正常化,并降低 RSNA 和 MAP。这些结果表明,PVN 中 AT(1)受体活性的增加有助于增强 CSAR 和肾血管性高血压大鼠过度的交感神经激活。