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首页> 外文期刊>Hypertension: An Official Journal of the American Heart Association >Angiotensin-(1-7) in the rostral ventrolateral medulla modulates enhanced cardiac sympathetic afferent reflex and sympathetic activation in renovascular hypertensive rats
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Angiotensin-(1-7) in the rostral ventrolateral medulla modulates enhanced cardiac sympathetic afferent reflex and sympathetic activation in renovascular hypertensive rats

机译：延髓腹侧延髓中的血管紧张素-（1-7）调节肾血管性高血压大鼠的心脏交感传入反射和交感激活

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Enhancement of the cardiac sympathetic afferent reflex (CSAR) contributes to sympathetic excitation in hypertension. The aim of the present study was to determine whether angiotensin (Ang)-(1-7) in the rostral ventrolateral medulla (RVLM) modulated the enhanced CSAR and sympathetic activation, and the signaling pathways that mediated these effects in the 2-kidney, 1-clip renovascular hypertension model. Cardiac sympathetic afferent reflex was evaluated using renal sympathetic nerve activity and mean arterial pressure responses to epicardial capsaicin application in anesthetized sinoaortic-denervated and cervical-vagotomized rats. RVLM microinjection of Ang-(1-7) induced greater increases in renal sympathetic nerve activity and mean arterial pressure, and greater enhancement in CSAR in 2-kidney, 1-clip rats than in sham-operated rats, which was blocked by Mas receptor antagonist A-779, adenylyl cyclase inhibitors SQ22536 and MDL-12,330A, and protein kinase A inhibitors rp-adenosine-3′, 5′-cyclic monophosphorothionate and H-89. Mas receptor expression in RVLM was increased in 2-kidney, 1-clip rats. Treatment with A-779, SQ22536, MDL-12,330A, rp-adenosine-3′,5′-cyclic monophosphorothionate, or H-89 in RVLM inhibited CSAR and decreased renal sympathetic nerve activity and mean arterial pressure in 2-kidney, 1-clip rats, whereas cAMP analogue dibutyryl-cAMP had the opposite effects. Ang-(1-7) in RVLM increased, whereas A-779 decreased the cAMP level and the epicardial capsaicin application-induced increases in the cAMP level in RVLM. These results indicate that Ang-(1-7) in the RVLM enhances the CSAR and increases the sympathetic outflow and blood pressure via Mas receptor activation. The increased endogenous Ang-(1-7) and Mas receptor activity in RVLM contributes to the enhanced CSAR and sympathetic activation in renovascular hypertension, and the cAMP-protein kinase A pathway is involved in these Ang-(1-7)-mediated effects in the RVLM.
机译：心脏交感神经反射（CSAR）的增强有助于高血压的交感神经兴奋。本研究的目的是确定在延髓腹侧延髓（RVLM）中的血管紧张素（Ang）-（1-7）是否能调节增强的CSAR和交感神经激活，以及在2型肾脏中介导这些作用的信号通路， 1-夹子肾血管性高血压模型。使用肾交感神经活动和平均动脉压对心外膜麻醉的和经颈迷走神经切断的麻醉大鼠的心外膜辣椒素应用的平均动脉压反应进行评估。 RVLM显微注射Ang-（1-7）诱导的肾交感神经活性和平均动脉压增加，与假手术的大鼠相比，肾虚的大鼠对2肾1夹的大鼠的CSAR的增强作用更大，后者被Mas受体阻断拮抗剂A-779，腺苷酸环化酶抑制剂SQ22536和MDL-12,330A以及蛋白激酶A抑制剂rp-腺苷-3'，5'-环一硫代磷酸酯和H-89。在2肾1夹大鼠中RVLM中的Mas受体表达增加。在RVLM中用A-779，SQ22536，MDL-12,330A，rp-腺苷3'，5'-环一硫代磷酸酯或H-89治疗可抑制CSAR并降低2位肾脏的肾交感神经活性和平均动脉压，1 -clip大鼠，而cAMP类似物dibutyryl-cAMP具有相反的作用。 RVLM中的Ang-（1-7）升高，而A-779降低了cAMP水平，而心外膜辣椒素的应用导致RVLM中的cAMP升高。这些结果表明，RVLM中的Ang-（1-7）通过Mas受体激活增强CSAR并增加交感神经流出和血压。 RVLM中内源性Ang-（1-7）和Mas受体活性的增加有助于肾血管性高血压中CSAR的增强和交感神经的激活，而cAMP-蛋白激酶A通路参与了这些Ang-（1-7）介导的作用在RVLM中。

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