Zhang F, Sun H-J, Xiong X-Q, Chen Q, Li Y-H, Kang Y-M, Wang J-J, Gao X-Y, Zhu G-Q
Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, China.
Acta Physiol (Oxf). 2014 Sep;212(1):17-27. doi: 10.1111/apha.12342. Epub 2014 Jul 18.
Apelin is a specific endogenous ligand of orphan G protein-coupled receptor APJ. This study was designed to determine the roles and mechanisms of apelin-13 and APJ in paraventricular nucleus (PVN) in renal sympathetic nerve activity (RSNA), arginine vasopressin (AVP) release and mean arterial pressure (MAP) in spontaneously hypertensive rats (SHR).
Acute experiment was carried out in 13-week-old male SHR and Wistar-Kyoto rats (WKY) under anaesthesia. RSNA and MAP responses to the PVN microinjection were determined. Apelin and APJ expressions were examined with quantitative real-time PCR and Western blot. AVP and noradrenaline were determined with ELISA. Osmotic minipumps were used for chronic PVN infusion in conscious WKY.
Apelin and APJ in the PVN were up-regulated in SHR. The PVN microinjection of apelin-13 increased, but APJ antagonist F13A decreased the RSNA, MAP, plasma noradrenaline and AVP levels in SHR. N-methyl-D-aspartate receptor (NMDAR) antagonist plus non-NMDAR antagonist abolished the apelin-13-induced sympathetic activation rather than AVP release. NMDAR antagonist or non-NMDAR antagonist alone attenuated the apelin-13-induced sympathetic activation. Chronic infusion of apelin-13 into the PVN in normotensive rats induced hypertension, increased plasma noradrenaline and AVP levels and promoted myocardial atrial natriuretic peptide and beta-myosin heavy chain mRNA expressions, two indicative markers of cardiac hypertrophy.
Apelin-13 and APJ in the PVN contribute to hypertension via sympathetic activation and AVP release in SHR. The sympatho-excitatory effect of apeline-13 is mediated by both NMDAR and non-NMDAR in the PVN. Persistent activation of APJ in the PVN induces hypertension.
Apelin是孤儿G蛋白偶联受体APJ的特异性内源性配体。本研究旨在确定apelin-13和APJ在自发性高血压大鼠（SHR）室旁核（PVN）中对肾交感神经活动（RSNA）、精氨酸加压素（AVP）释放及平均动脉压（MAP）的作用和机制。
对13周龄雄性SHR和Wistar-Kyoto大鼠（WKY）进行麻醉下的急性实验。测定对PVN微量注射的RSNA和MAP反应。采用定量实时PCR和蛋白质印迹法检测Apelin和APJ的表达。用酶联免疫吸附测定法测定AVP和去甲肾上腺素。在清醒的WKY中使用渗透微型泵进行PVN慢性输注。
SHR中PVN的Apelin和APJ上调。向PVN微量注射apelin-13可使SHR的RSNA、MAP、血浆去甲肾上腺素和AVP水平升高，但APJ拮抗剂F13A可使其降低。N-甲基-D-天冬氨酸受体（NMDAR）拮抗剂加非NMDAR拮抗剂可消除apelin-13诱导的交感神经激活，而非AVP释放。单独使用NMDAR拮抗剂或非NMDAR拮抗剂可减弱apelin-13诱导的交感神经激活。向正常血压大鼠的PVN慢性输注apelin-13可导致高血压，增加血浆去甲肾上腺素和AVP水平，并促进心肌心钠素和β-肌球蛋白重链mRNA表达，这是心脏肥大的两个指示性标志物。
PVN中的apelin-13和APJ通过交感神经激活和AVP释放参与SHR的高血压形成。apelin-13的交感兴奋作用由PVN中的NMDAR和非NMDAR介导。PVN中APJ的持续激活可诱发高血压。
