Alamandine injected into the paraventricular nucleus increases blood pressure and sympathetic activation in spontaneously hypertensive rats
Alamandine injected into the paraventricular nucleus increases blood pressure and sympathetic activation in spontaneously hypertensive rats
复制标题
室旁核注射阿拉曼定可增加自发性高血压大鼠的血压和交感神经激活
DOI：
10.1016/j.peptides.2018.03.014
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发表时间：
2018-05-01
期刊：
影响因子：
3
通讯作者：
Li, Peng
中科院分区：
文献类型：
--
作者：
Shen, Yi-Hui;Chen, Xi-Ru;Li, Peng
阿拉芒丁是肾素-血管紧张素系统(RAS)中新发现的一种新成分，已被证明在神经系统的某些区域发挥血管活性作用。本研究调查了向下丘脑室旁核(PVN)注射丙烷胺是否调节血压和交感神经活动。记录麻醉大鼠的平均动脉压(MAP)和肾交感神经活动(RSNA)。下丘脑室旁核微量注射丙烷胺可使Wistar-京都(WKY)大鼠和自发性高血压大鼠(SHR)的MAP和RSNA升高，但SHR的升高幅度更大。上述作用可被丙氨酸受体Mas相关G蛋白偶联受体、D成员(MRgD)拮抗剂D-Pro7-Ang-(1-7)、腺苷环化酶(AC)抑制剂SQ22536和蛋白激酶A(PKA)抑制剂RP-腺苷-3‘，5’-环磷酸腺苷(RP-cAMP)阻断。在PVN中单独应用D-Pro7-Ang-(1-7)、SQ22536或RP-cAMP可降低SHR的MAP和RSNA。单用cAMP可增加MAP和RSNA，cAMP预处理可增强丙烷胺的作用。这些结果表明，下丘脑室旁核内微量注射丙烷胺可通过mRgD和cAMP-PKA通路增加血压和交感神经流出。
Alamandine is a newly discovered new component of the renin-angiotensin (Ang) system (RAS) that has been shown to exert vasoactive effects in some areas of the nervous system. The present study investigated whether administration of alamandine to the hypothalamic paraventricular nucleus (PVN) modulates blood pressure and sympathetic activity. Mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were recorded in anaesthetized rats. PVN microinjection of alamandine increased MAP and RSNA both in Wistar-Kyoto (WKY) rats and in spontaneously hypertensive rats (SHRs), but to a greater extent in SHRs. Moreover, these effects were blocked by pretreatment with alamandine receptor Mas-related G-protein-coupled receptor, member D (MrgD) antagonist D-Pro7-Ang-(1-7), adenylyl cyclase (AC) inhibitor SQ22536, and protein kinase A (PKA) inhibitor rp-adenosine-3', 5'-cyclic monophosphorothionate (Rp-cAMP). Treatment with D-Pro7-Ang-(1-7), SQ22536, or Rp-cAMP alone in PVN decreased MAP and RSNA in the SHRs. Conversely cAMP alone increased MAP and RSNA, and pretreatment with cAMP enhanced alamandine's effects. These results indicate that microinjection of alamandine into the PVN increases blood pressure and sympathetic outflow via MrgD and the cAMP-PKA pathway.