Angiotensin II is a vasoconstrictor and the main bioactive peptide of the renin/Angiotensin system. Angiotensin II human plays a central role in the regulation of human blood pressure, mainly through Angiotensin II and G protein-coupled receptors(GPCRs) Angiotensin II type 1 receptor (AT1R) and Angiotensin II type 2 receptor (AT2R) interact to mediate[1].
Human induces capillary formation in endothelial cells through a LOX-1-dependent redox-sensitive pathway. Angiotensin II (1 nM) induces the expression of LOX-1 and VEGF and enhances capillary formation from human coronary endothelial cells in Matrigel assay[3,4].Angiotensin II helps to regulate overall renal tubular reabsorption of salt and water, Angiotensin II directly stimulates epithelial sodium channel activity through an AT1 receptor-dependent mechanism[8].Angiotensin II Human induces the growth of vascular smooth muscle cells, increases the synthesis of collagen type I and III in fibroblasts, leads to the thickening of the vascular wall and myocardium, and induces fibrosis. Angiotensin II also induces apoptosis[2].The effects of Angiotensin II to increase blood pressure are mediated by AT1 receptors[1], and these receptors are expressed in a variety of organ systems thought to play key roles in blood pressure homeostasis, including the heart, kidney, blood vessels, adrenal glands, and cardiovascular control centers in the brain[5]. In the brain, intraventricular injection of Angiotensin II causes a dramatic pressor response that is mediated by AT1A receptors[6].
In mice, AT1 receptors in the kidney are primarily responsible for the actions of Angiotensin II to cause hypertension[7]. Angiotensin II induction of NETosis in vitro via ROS/ peptidyl arginine deiminase type 4 and autophagy dependent pathways In EH patients initiated with Angiotensin II receptor blockers, circulating NETs and thrombin production levels were significantly reduced, whereas their plasma was unable to trigger procoagulant NETs [9].
References:
[1]: de Gasparo M, Catt KJ, et,al. International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev. 2000 Sep;52(3):415-72. PMID: 10977869.
[2]: Fyhrquist F, Mets?rinne K, et,al. Role of angiotensin II in blood pressure regulation and in the pathophysiology of cardiovascular disorders. J Hum Hypertens. 1995 Nov;9 Suppl 5:S19-24. PMID: 8583476.
[3]: Hu C, Dandapat A, et,al. Angiotensin II induces capillary formation from endothelial cells via the LOX-1 dependent redox-sensitive pathway. Hypertension. 2007 Nov;50(5):952-7. doi: 10.1161/HYPERTENSIONAHA.107.096446. Epub 2007 Sep 24. PMID: 17893372.
[4]: Nabah YN, Mateo T, et,al. Angiotensin II induces neutrophil accumulation in vivo through generation and release of CXC chemokines. Circulation. 2004 Dec 7;110(23):3581-6. doi: 10.1161/01.CIR.0000148824.93600.F3. Epub 2004 Nov 29. PMID: 15569833.
[5]: Shanmugam S, Sandberg K. Ontogeny of angiotensin II receptors. Cell Biol Int. 1996 Mar;20(3):169-76. doi: 10.1006/cbir.1996.0021. PMID: 8673065.
[6]: Davisson RL, Oliverio MI, et,al. Divergent functions of angiotensin II receptor isoforms in the brain. J Clin Invest. 2000 Jul;106(1):103-6. doi: 10.1172/JCI10022. PMID: 10880053; PMCID: PMC314366.
[7]: Crowley SD, Gurley SB, et,al. Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17985-90. doi: 10.1073/pnas.0605545103. Epub 2006 Nov 7. PMID: 17090678; PMCID: PMC1693859.
[8]: Peti-Peterdi J, Warnock DG, et,al. Angiotensin II directly stimulates ENaC activity in the cortical collecting duct via AT(1) receptors. J Am Soc Nephrol. 2002 May;13(5):1131-5. doi: 10.1097/01.asn.0000013292.78621.fd. PMID: 11960999.
[9]: Chrysanthopoulou A, Gkaliagkousi E, et,al. Angiotensin II triggers release of neutrophil extracellular traps, linking thromboinflammation with essential hypertension. JCI Insight. 2021 Sep 22;6(18):e148668. doi: 10.1172/jci.insight.148668. PMID: 34324440; PMCID: PMC8492353.
血管紧张素II是肾素/血管紧张素系统的主要生物活性肽和一种血管收缩剂。在人体内，血管紧张素II通过与G蛋白偶联受体（GPCR）—— 血管紧张素II类型1受体（AT1R）和血管紧张素II类型2受体（AT2R）相互作用来调节人类的血压，其中AT1R和AT2R起到中心作用[1]。
人体通过一种LOX-1依赖的氧化还原敏感途径诱导内皮细胞形成毛细血管。肾素-血管紧张素系统中的肾素酶会将肾素转化为血管紧张素I，而后者再被转化为血管紧张素II（浓度为1纳摩尔）。这个过程会引起LOX-1和VEGF表达增加，并促进人类冠状动脉内皮细胞在Matrigel试验中形成毛细血管[3,4]。此外，肾上腺髓质分泌的去甲肾上腺素也能刺激AT1受体，从而使得心率、收缩压和舒张压升高。
同时，肾上腺髓质分泌的去甲肾上腺素也可以直接作用于远端小球旁通道及近曲小管等部位，在调节整体盐水重吸收方面发挥作用。Angiotensin II还能够诱导平滑肌细胞生长、增加成纤维细胞合成Ⅰ型和Ⅲ型胶原，并导致血管壁和心室壁变厚以及引起纤维化反应。此外，Angiotensin II还能够诱导细胞凋亡[2]。
肾素-血管紧张素系统通过AT1受体介导增加血压的效应在多个器官系统中发挥作用，这些器官被认为在血压稳态调节中起着关键作用，包括心脏、肾脏、血管、肾上腺和控制心血管的大脑区域[5]。在大脑中，注射Angiotensin II到侧脑室会引起剧烈的升压反应，并且这种反应是由AT1A受体介导的[6]。
在小鼠中，肾脏中的AT1受体主要负责血管紧张素II引起高血压的作用。通过ROS/ peptidyl arginine deiminase type 4和自噬依赖途径，在体外诱导Angiotensin II NETosis。在使用Angiotensin II受体拮抗剂开始治疗的EH患者中，循环NETs和凝血酶产生水平显着降低，而它们的血浆无法触发促凝状态的NETs。