Intermedin in the paraventricular nucleus attenuates cardiac sympathetic afferent reflex in chronic heart failure rats.
Intermedin in the paraventricular nucleus attenuates cardiac sympathetic afferent reflex in chronic heart failure rats.
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DOI：
10.1371/journal.pone.0094234
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhou YB
中科院分区：
文献类型：
--
作者：
Gan XB;Sun HJ;Chen D;Zhang LL;Zhou H;Chen LY;Zhou YB
Intermedin （IMD）是降钙素/降钙素基因相关肽（CGRP）家族的成员，与肾上腺髓质素（AM）和amylin一起。它广泛分布于中枢神经系统，特别是下丘脑室旁核。慢性心力衰竭（CHF）大鼠心脏交感传入反射（CSAR）增强。本研究的目的是确定PVN内IMD对CHF大鼠CSAR的影响及其相关机制。采用左冠状动脉降支结扎术或假手术诱导CHF。记录肾交感神经活动（RSNA）、平均动脉压（MAP）和心率（HR）。通过RSNA和MAP对心外膜应用辣椒素的反应来评估CSAR。急性实验于冠脉结扎或假手术后8周麻醉下进行。CHF大鼠PVN内IMD和血管紧张素II （Ang II）水平上调。双侧PVN显微注射IMD导致CHF大鼠CSAR、基线RSNA和MAP的下降幅度大于Sham大鼠。AM受体拮抗剂AM22-52对IMD所致的CSAR降低有抑制作用，而CGRP受体拮抗剂CGRP8-37对IMD所致的CSAR降低无抑制作用。PVN中的Ang II可显著提高Sham和CHF大鼠的CSAR和超氧阴离子水平，而IMD或tempol（一种超氧阴离子清除剂）预处理PVN可抑制这一作用。PVN内IMD通过AM受体抑制CSAR，减弱Ang II对CHF大鼠CSAR及超氧阴离子水平的影响。PVN超氧阴离子参与了IMD对Ang ii诱导的CSAR反应的减弱作用。
Intermedin (IMD) is a member of calcitonin/calcitonin gene-related peptide (CGRP) family together with adrenomedullin (AM) and amylin. It has a wide distribution in the central nervous system (CNS) especially in hypothalamic paraventricular nucleus (PVN). Cardiac sympathetic afferent reflex (CSAR) is enhanced in chronic heart failure (CHF) rats. The aim of this study is to determine the effect of IMD in the PVN on CSAR and its related mechanisms in CHF rats. Rats were subjected to left descending coronary artery ligation to induce CHF or sham-operation (Sham). Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were recorded. CSAR was evaluated by the RSNA and MAP responses to epicardial application of capsaicin. Acute experiments were carried out 8 weeks after coronary ligation or sham surgery under anesthesia. IMD and angiotensin II (Ang II) levels in the PVN were up-regulated in CHF rats. Bilateral PVN microinjection of IMD caused greater decreases in CSAR and the baseline RSNA and MAP in CHF rats than those in Sham rats. The decrease of CSAR caused by IMD was prevented by pretreatment with AM receptor antagonist AM22-52, but not CGRP receptor antagonist CGRP8-37. Ang II in the PVN significantly enhanced CSAR and superoxide anions level, which was inhibited by PVN pretreatment with IMD or tempol (a superoxide anions scavenger) in Sham and CHF rats. IMD in the PVN inhibits CSAR via AM receptor, and attenuates the effects of Ang II on CSAR and superoxide anions level in CHF rats. PVN superoxide anions involve in the effect of IMD on attenuating Ang II-induced CSAR response.
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