ERK1/2 Mediated The Vasodilatation of Apelin-13 on Vascular Rings of Spontanously Hypertensive Rat <I>in vitro</I>*

Abstract

李兰芳 2) 苏桃 2) 陈临溪 2)***( 1) 南华大学附属第一医院心内科，衡阳 421001； 2) 南华大学药物药理研究所，衡阳 421001) 摘要 研究自发性高血压大鼠(spontanouslyhypertensiverat，SHR)离体血管环对 G 蛋白偶联受体 APJ 的内源性配体 apelin-13 的血管收缩与舒张反应及其与一氧化氮(NO)和 ERK1/2 通路关系． 采用离体血管环体外灌流方法用 Power-Lab 生物信息采集 仪检测血管环的张力． 实验分组如下：新福林(Phenylephrine，PE)组，乙酰胆碱(acetylcholine， Ach)组，apelin-13 组， apelin-13 + PE 组，apelin-13 + Ach 组，PD98059(ERK1/2 抑制剂)+ PE 组，PD98059 + Ach 组，LNNA(L-nitro-arginine，硝基左 旋精氨酸，一氧化氮合酶抑制剂) +PE 组，LNNA+Ach 组，apelin-13(预孵育) + PD98059 + PE 组，apelin-13(预孵育)+PD98059+ Ach 组，apelin-13(预孵育)+ LNNA + PE 组和 apelin-13(预孵育)+LNNA + Ach 组，以 WKY 大鼠血管环为对照组． 培养大鼠血 管平滑肌细胞，Westernblot 检测 ERK1/2 蛋白表达． 结果显示：a． apelin-13 对于有内皮的血管表现出浓度依赖性舒张作用， 血管舒张百分比 SHR<WKY 大鼠，而对于去除内皮血管，apelin-13 则表现出收缩血管的作用，且收缩张力 SHR>WKY 大 鼠，apelin-13 预孵育，能减少 SHR 和 WKY 大鼠血管对新福林的缩血管反应性，增加对乙酰胆碱的舒张反应性；b． NOS 抑 制剂 LNNA 阻断 NO 形成后，血管环对 apelin-13 的舒张反应明显抑制，且 SHR 组较 WKY 组对 apelin 的舒张反应减少更明 显，提示 apelin-13 的舒血管效应至少部分依赖 NO 通路，而 SHR 高血压大鼠 NO 通路障碍减弱了 apelin 对血管的舒张作用； c． ERK1/2 抑制剂 PD98059 预孵育后血管环对 apelin-13 表现出浓度依赖性的收缩，与去除内皮后 apelin-13 的收缩血管效应 趋势一致，血管收缩张力 SHR＞ WKY 大鼠，PD98059 逆转了 apelin-13 引起的血管舒张效应；d． Apelin-13 促大鼠 VSMCs ERK1/2 磷酸化增加并呈剂量依赖性和时间依赖性，ERK1/2 抑制剂 PD98059 可以减少 apelin-13 诱导 ERK1/2 的磷酸化． 结 果表明，自发性高血压大鼠离体血管环对 apelin-13 舒张反应性降低， NO 通路和 ERK1/2 通路介导了 apelin-13 的舒张血管 作用． 关键词 apelin-13，APJ，一氧化氮合酶，自发性高血压大鼠，细胞外信号调节激酶 1/2(ERK1/2) 学科分类号 Q4，R36，R9

ROS‐Autophagy pathway mediates monocytes‐human umbilical vein endothelial cells adhesion induced by apelin‐13

“…Our laboratory has been studied the effect of apelin/APJ on the cardiovascular system for several years. We demonstrated that apelin-13 reduced blood pressure (Li et al, 2007) and promoted vasodilatation of vascular rings on spontaneously hypertension rat in vitro which was mediated by extracellular signal-regulated kinases 1 and 2 (ERK1/2) (Liu et al, 2009). Besides, we also reported that apelin-13 promoted cardiomyocytes (Xie et al, 2015).…”

ERK1/2 mediates lung adenocarcinoma cell proliferation and autophagy induced by apelin-13

“…Apelins and APJ are widely expressed in animal and human heart, lung, kidney, brain, liver, breast, and skeletal muscle and abundantly found in cardiovascular, brain, lung, and breast cancers. Previous studies have shown that apelin/APJ system has effects on the function of cardiovascular system [4], has the functional and histopathological protective effects against renal ischemia/ reperfusion injury [5], and has the effect of analgesia [6]. In addition, apelin/APJ system is involved in many processes such as regulation of the release of hormone and metabolism [7], regulation of cell proliferation, migration, and apoptosis [8], and reduction of pulmonary inflammation and fibrin deposition [9].…”

14-3-3 mediates apelin-13-induced enhancement of adhesion of monocytes to human umbilical vein endothelial cells

“…Animal and human studies suggested that it might play a role in the pathogenesis of heart failure by modulating the harmful effects of Ang II [8,9]. The diastolic reactivity of apelin in ex vivo vascular rings of SHR (spontanously hypertensive rat) is reduced and the effect is mediated by NO pathway and the ERK1/2 pathway [10]. High levels of both APJ and apelin mRNA are found in cardiac myocytes, vascular smooth muscle, and endothelial cells of large conduit arteries, coronary vessels, and endocardium of the right atrium [11 -13].…”