Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, China.
Nitric Oxide. 2019 Jul 1;88:1-9. doi: 10.1016/j.niox.2019.03.007. Epub 2019 Mar 14.
Enhanced vasoconstriction and decreased vasodilatation due to endothelial dysfunction contribute to the progression of hypertension. Angiotensin (Ang)-(1-7) plays important roles in regulating the cardiovascular activity. The current study aimed to investigate the roles of Ang-(1-7) in modulating blood pressure, vascular tension and its signal pathway in spontaneously hypertensive rats (SHR). The effects of intravenous injection of drugs were determined in rats with anesthesia in vivo. Mesenteric artery (MA), coronary artery (CA) and pulmonary artery (PA) were isolated from rats and isometric tension measurements in arteries were performed. Compared with Wistar-Kyoto rats (WKY), the high K induced vasoconstriction was enhanced and acetylcholine-induced vasodilatation were attenuated in the MA, CA and PA in SHR. Intravenous injection of Ang-(1-7) decreased, while A-779 increased mean arterial pressure and abolished the hypotensive effect of Ang-(1-7) in SHR. Ang-(1-7) caused dose-dependent relaxation in MA, CA and PA in SHR, which was inhibited by pretreatment with Mas receptor antagonist A-779, nitric oxide (NO) synthase inhibitor l-NAME, guanylate cyclase inhibitor ODQ and protein kinase G (PKG) inhibitor DT-2. The Mas receptor expression, NO, cGMP and PKG levels of the three above arteries of SHR were lower than that of WKY. Ang-(1-7) increased the NO, cGMP and PKG levels in arteries from SHR, which was blocked by A-779. Activation of the Mas receptor by Ang-(1-7) relaxes the MA, CA, and PA through the NO-cGMP-PKG pathway, which contributes to the decrease of arterial pressure in SHR.
由于内皮功能障碍导致的血管收缩增强和血管舒张减弱，促进了高血压的进展。血管紧张素（Ang）-（1-7）在调节心血管活动方面发挥着重要作用。本研究旨在探讨 Ang-（1-7）在调节自发性高血压大鼠（SHR）血压、血管张力及其信号通路中的作用。在体内麻醉大鼠中，通过静脉注射药物来确定药物的作用。从大鼠中分离出肠系膜动脉（MA）、冠状动脉（CA）和肺动脉（PA），并对动脉进行等长张力测量。与 Wistar-Kyoto 大鼠（WKY）相比，SHR 的 MA、CA 和 PA 中高 K 诱导的血管收缩增强，乙酰胆碱诱导的血管舒张减弱。静脉注射 Ang-（1-7）可降低 SHR 的平均动脉压，而 A-779 可消除 Ang-（1-7）的降压作用。Ang-（1-7）可引起 SHR 的 MA、CA 和 PA 产生剂量依赖性的舒张作用，这种作用可被 Mas 受体拮抗剂 A-779、一氧化氮（NO）合酶抑制剂 l-NAME、鸟苷酸环化酶抑制剂 ODQ 和蛋白激酶 G（PKG）抑制剂 DT-2 预处理所抑制。SHR 的上述三条动脉的 Mas 受体表达、NO、cGMP 和 PKG 水平均低于 WKY。Ang-（1-7）可增加 SHR 动脉中的 NO、cGMP 和 PKG 水平，而 A-779 可阻断这一作用。Ang-（1-7）通过激活 Mas 受体，通过 NO-cGMP-PKG 途径舒张 MA、CA 和 PA，从而有助于降低 SHR 的动脉压。
