室旁核内血管紧张素 II 和血管紧张素-(1-7)调节肾血管性高血压大鼠心脏交感传入反射。
Angiotensin II and angiotensin-(1-7) in paraventricular nucleus modulate cardiac sympathetic afferent reflex in renovascular hypertensive rats.
机构信息
Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
出版信息
PLoS One. 2012;7(12):e52557. doi: 10.1371/journal.pone.0052557. Epub 2012 Dec 20.
BACKGROUND
The enhanced cardiac sympathetic afferent reflex (CSAR) is involved in the sympathetic activation that contributes to the pathogenesis and progression of hypertension. Activation of AT(1) receptors by angiotension (Ang) II in the paraventricular nucleus (PVN) augments the enhanced CSAR and sympathetic outflow in hypertension. The present study is designed to determine whether Ang-(1-7) in PVN plays the similar roles as Ang II and the interaction between Ang-(1-7) and Ang II on CSAR in renovascular hypertension.
METHODOLOGY/PRINCIPAL FINDINGS: The two-kidney, one-clip (2K1C) method was used to induce renovascular hypertension. The CSAR was evaluated by the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) responses to epicardial application of capsaicin in sinoaortic-denervated and cervical-vagotomized rats with urethane and α-chloralose anesthesia. Either Ang II or Ang-(1-7) in PVN caused greater increases in RSNA and MAP, and enhancement in CSAR in 2K1C rats than in sham-operated (Sham) rats. Mas receptor antagonist A-779 and AT(1) receptor antagonist losartan induced opposite effects to Ang-(1-7) or Ang II respectively in 2K1C rats, but losartan had no effects in Sham rats. Losartan but not the A-779 abolished the effects of Ang II, while A-779 but not the losartan blocked the effects of Ang-(1-7). PVN pretreatment with Ang-(1-7) dose-dependently augmented the RSNA, MAP, and CSAR responses to the Ang II in 2K1C rats. Ang II level, AT(1) receptor and Mas receptor protein expression in PVN increased in 2K1C rats compared with Sham rats but Ang-(1-7) level did not.
CONCLUSIONS
Ang-(1-7) in PVN is as effective as Ang II in enhancing the CSAR and increasing sympathetic outflow and both endogenous Ang-(1-7) and Ang II in PVN contribute to the enhanced CSAR and sympathetic outflow in renovascular hypertension. Ang-(1-7) in PVN potentiates the effects of Ang II in renovascular hypertension.
背景
增强的心脏交感传入反射（CSAR）参与了交感神经激活，这有助于高血压的发病机制和进展。血管紧张素（Ang）II 在室旁核（PVN）中激活 AT1 受体可增强高血压时增强的 CSAR 和交感传出。本研究旨在确定 PVN 中的 Ang-(1-7) 是否发挥与 Ang II 相似的作用，以及 Ang-(1-7) 和 Ang II 之间在肾血管性高血压中的 CSAR 相互作用。
方法/主要发现：采用双肾一夹（2K1C）方法诱导肾血管性高血压。在乌拉坦和α-氯醛糖麻醉下，通过心外膜应用辣椒素评估肾交感神经活性（RSNA）和平均动脉压（MAP）对 CSAR 的反应，以评估 sinoaortic 去神经和颈静脉切断大鼠的 CSAR。与假手术（Sham）大鼠相比，PVN 中的 Ang II 或 Ang-(1-7) 引起的 RSNA 和 MAP 增加更大，并增强了 2K1C 大鼠的 CSAR。Mas 受体拮抗剂 A-779 和 AT1 受体拮抗剂氯沙坦分别在 2K1C 大鼠中引起与 Ang-(1-7) 或 Ang II 相反的作用，但氯沙坦在 Sham 大鼠中没有作用。氯沙坦而非 A-779 消除了 Ang II 的作用，而 A-779 而非氯沙坦阻断了 Ang-(1-7) 的作用。PVN 预处理剂量依赖性地增强了 2K1C 大鼠 Ang II 对 RSNA、MAP 和 CSAR 的反应。与 Sham 大鼠相比，2K1C 大鼠 PVN 中的 Ang II 水平、AT1 受体和 Mas 受体蛋白表达增加，但 Ang-(1-7) 水平没有增加。
结论
PVN 中的 Ang-(1-7) 与 Ang II 一样有效增强 CSAR 和增加交感传出，PVN 中的内源性 Ang-(1-7) 和 Ang II 均有助于肾血管性高血压时增强的 CSAR 和交感传出。PVN 中的 Ang-(1-7) 增强了肾血管性高血压中 Ang II 的作用。
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