Wang Han-Jun, Zhang Feng, Zhang Ying, Gao Xing-Ya, Wang Wei, Zhu Guo-Qing
Department of Physiology, Nanjing Medical University, Nanjing 210029, P.R. China.
Auton Neurosci. 2005 Aug 31;121(1-2):56-63. doi: 10.1016/j.autneu.2005.07.003.
Our previous studies have shown that the cardiac sympathetic afferent reflex (CSAR) was enhanced in the chronic heart failure in dogs and rats. Exogenous angiotensin II (Ang II) in the paraventricular nucleus (PVN) potentiated this reflex which was mediated by AT1 receptor. The aim of the present study was to determine if the abnormal endogenous Ang II and AT1 receptor in the PVN were responsible for the enhanced CSAR in rats with coronary ligation-induced chronic heart failure (CHF). Under urethane and alpha-chloralose anesthesia, mean arterial pressure, heart rate and renal sympathetic nerve activity (RSNA) were recorded in sino-aortic denervated and cervical vagotomized CHF and sham-operated rats. The effects of bilateral microinjection of AT1 receptor antagonist losartan and angiotensin converting enzyme inhibitor captopril on the CSAR evoked by epicardial application of bradykinin (BK, 0.04 and 0.4 microg) were determined respectively. Both AT1 receptor mRNA and AT1 receptor protein in the PVN were measured. Bilateral microinjection of either captopril (10 nmol) or losartan (50 nmol) into the PVN inhibited the enhanced CSAR evoked by BK in rats with CHF, but had no significant effects in sham-operated rats. AT1 receptor protein in the PVN significantly increased in CHF rats compared with sham-operated rats. These results indicated that either decrease of Ang II or blockage of AT1 receptor in the PVN normalized the enhanced CSAR evoked by epicardial application of BK in rats with CHF, and that increased expression of AT1 receptor in the PVN contributed to the enhanced CSAR in the CHF state.
我们之前的研究表明，犬和大鼠慢性心力衰竭时心脏交感神经传入反射（CSAR）增强。室旁核（PVN）中的外源性血管紧张素II（Ang II）增强了由AT1受体介导的该反射。本研究的目的是确定PVN中异常的内源性Ang II和AT1受体是否与冠状动脉结扎诱导的慢性心力衰竭（CHF）大鼠CSAR增强有关。在乌拉坦和α-氯醛糖麻醉下，记录了去窦主动脉和颈迷走神经切断的CHF大鼠及假手术大鼠的平均动脉压、心率和肾交感神经活动（RSNA）。分别测定了双侧微量注射AT1受体拮抗剂氯沙坦和血管紧张素转换酶抑制剂卡托普利对心外膜应用缓激肽（BK，0.04和0.4微克）诱发的CSAR的影响。检测了PVN中AT1受体mRNA和AT1受体蛋白。双侧向PVN微量注射卡托普利（10纳摩尔）或氯沙坦（50纳摩尔）均可抑制CHF大鼠中BK诱发的增强的CSAR，但对假手术大鼠无显著影响。与假手术大鼠相比，CHF大鼠PVN中的AT1受体蛋白显著增加。这些结果表明，PVN中Ang II的减少或AT1受体的阻断可使CHF大鼠心外膜应用BK诱发的增强的CSAR恢复正常，且PVN中AT1受体表达增加导致CHF状态下CSAR增强。
