Blood Vessels

Ang-(1-7) and Vessels
  • Walyria O. Sampaio
  • Rhian M. TouyzEmail author


This chapter focuses on the vasoprotective effects of Ang-(1-7). The vasculature is a key site of Ang-(1-7) synthesis and actions. One of the earliest functional effects described for Ang-(1-7) in the cardiovascular system was its ability to induce vasodilation. Since then, growing evidence has demonstrated multiple vasoprotective properties for Ang-(1-7) in isolated vessels, cell culture, as well as in vivo. Ang-(1-7) mediates effects through receptor Mas, a G protein-coupled receptor. In addition to its widespread vasodilatory activity, Ang-(1-7) and receptor Mas are functionally present in vascular smooth muscle cells and platelets, where Ang-(1-7) signaling through Mas induces anti-inflammatory, anti-proliferative, and antithrombotic effects. The main known vascular effects of Ang-(1-7) are described in Fig. 1.


Angiotensin peptides Mas receptor Endothelium Vascular smooth muscle cells Signal transduction Angiotensin-(1-7) Endothelial function Vasodilation 


  1. 1.
    Santos RA, Brosnihan KB, Jacobsen DW, DiCorleto PE, Ferrario CM. Production of angiotensin-(1-7) by human vascular endothelium. Hypertension. 1992;19:II56–61.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    le Tran Y, Forster C. Angiotensin-(1-7) and the rat aorta: modulation by the endothelium. J Cardiovasc Pharmacol. 1997;30(5):676–82.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Lemos VS, Cortes SF, Silva DM, Campgnole-Santos MJ, Santos RA. Angiotensin-(1-7) is involved in the endothelium-dependent modulation of phenylefrine-induced contraction in the aorta of m-Ren transgenic rats. Br J Pharmacol. 2002;135:1743–8.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Brosnihan KB, Li P, Ferrario CM. Angiotensin-(1-7) dilates canine coronary arteries through kinins and nitric oxide. Hypertension. 1996;27(3 Pt2):523–8.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Pörsti I, Bara AT, Busse R, Hecker M. Release of nitric oxide by angiotensin-(1-7) from porcine coronary endothelium: implications for a novel angiotensin receptor. Br J Pharmacol. 1994;111:652–4.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Feterik K, Smith L, Katusic ZS. Angiotensin-(1-7) causes endothelium-dependent relaxation in canine middle cerebral artery. Brain Res. 2000;873:75–82.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Meng W, Busija DW. Comparative effects of angiotensin-(1-7) and angiotensin II on piglet pial arterioles. Stroke. 1993;24:2041–5.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Ren Y, Garvin JL, Carretero OA. Vasodilator action of angiotensin-(1-7) on isolated rabbit afferent arterioles. Hypertension. 2002;39:799–802.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Oliveira MA, Fortes ZB, Santos RAS, Khosla MC, Carvalho MHC. Synergistic effect of angiotensin-(1-7) on bradykinin arteriolar dilation in vivo. Peptides. 1999;20:1195–201.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Fernandes L, Fortes ZB, Nigro D, Tostes RCA, Santos RAS, Carvalho MHC. Potentiation of bradykinin by angiotensin-(1-7) on arterioles of spontaneously hypertensive rats studied in vivo. Hypertension. 2001;37:703–9.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    de Moraes PL, Kangussu LM, Castro CH, Almeida AP, Santos RAS, Ferreira AJ. Vasodilator effect of angiotensin-(1-7) on vascular coronary bed of rats: role of Mas, ACE and ACE2. Protein Pept Lett. 2017;24(9):869–75.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Santos RAS, Passaglio KT, Pesquero JB. Bader M, Simões e Silva AC. Interactions between kinins and angiotensin-(1-7) in kidney and blood vessels. Hypertension. 2001;38:660–4.CrossRefGoogle Scholar
  13. 13.
    van Twist DJ, Houben AJ, de Haan MW, Mostard GJ, Kroon AA, de Leeuw PW. Angiotensin-(1-7)-induced renal vasodilation in hypertensive humans is attenuated by low sodium intake and angiotensin II co-infusion. Hypertension. 2013;62:789–93.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 14.
    Grace JA, Klein S, Herath CB, Granzow M, Schierwagen R, Masing N, Walther T, Sauerbruch T, Burrell LM, Angus PW, Trebicka J. Activation of the MAS receptor by angiotensin-(1-7) in the renin–angiotensin system mediates mesenteric vasodilatation in cirrhosis. Gastroenterology. 2013;145(4):874–84.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Raffai G, Lombard JH. Angiotensin-(1-7) selectively induces relaxation and modulates endothelium-dependent dilation in mesenteric arteries of salt-fed rats. J Vasc Res. 2016;53(1–2):105–18.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Yuan L, Li Y, Li G, Song Y, Gong X. Ang(1-7) treatment attenuates β-cell dysfunction by improving pancreatic microcirculation in a rat model of type 2 diabetes. J Endocrinol Investig. 2013;36(11):931–7.Google Scholar
  17. 17.
    Dincă M, Dumitriu IL, Gurzu MB, Slătineanu SM, Foia L, Vâţă L, Cojocaru E, Petrescu G. Ghrelin and Ang 1-7 have cumulative vasodilatory effects on pulmonary vessels. Rev Med Chir Soc Med Nat Iasi. 2010;114(3):803–7.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Pernomian L, Gomes MS, Restini CB, de Oliveira AM. MAS-mediated antioxidant effects restore the functionality of angiotensin converting enzyme 2-angiotensin-(1-7)-MAS axis in diabetic rat carotid. Biomed Res Int. 2014;2014:640329.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Sampaio WO, Nascimento AA, Santos RA. Systemic and regional hemodynamic effects of angiotensin-(1-7) in rats. Am J Physiol Heart Circ Physiol. 2003;284(6):H1985–94.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Botelho-Santos GA, Sampaio WO, Reudelhuber TL, Bader M, Campagnole-Santos MJ, Santos RAS. Expression of an angiotensin-(1-7)-producing fusion protein in rats induced marked changes in regional vascular resistance. Am J Physiol Heart Circ Physiol. 2007;292(5):H2485–90.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Botelho-Santos GA, Bader M, Alenina N, Santos RA. Altered regional blood flow distribution in Mas-deficient mice. Ther Adv Cardiovasc Dis. 2012;6(5):201–11.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Hisatake S, Kiuchi S, Kabuki T, Oka T, Dobashi S, Ikeda T. Serum angiotensin-converting enzyme 2 concentration and angiotensin-(1-7) concentration in patients with acute heart failure patients requiring emergency hospitalization. Heart Vessel. 2017;32(3):303–8.CrossRefGoogle Scholar
  23. 23.
    Van Twist DJ, Houben AJ, De Haan MW, Mostard GJ, De Leeuw PW, Kroon AA. Angiotensin-(1-7)-induced renal vasodilation is reduced in human kidneys with renal artery stenosis. J Hypertens. 2014;32(12):2428–32; discussion 2432PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Kocks MJ, Lely AT, Boomsma F, Jong PE, Navis G. Sodium status and angiotensin-converting enzyme inhibition: effects on plasma angiotensin-(1-7) in healthy man. J Hypertens. 2005;23:597–602.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    van der Wouden EA, Ochodnický P, van Dokkum RP, Roks AJ, Deelman LE, de Zeeuw D, et al. The role of angiotensin(1-7) in renal vasculature of the rat. J Hypertens. 2006;24:1971–8.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Mendonça L, Mendes-Ferreira P, Bento-Leite A, Cerqueira R, Amorim MJ, Pinho P, Brás-Silva C, Leite-Moreira AF, Castro-Chaves P. Angiotensin-(1-7) modulates angiotensin II-induced vasoconstriction in human mammary artery. Cardiovasc Drugs Ther. 2014;28(6):513–22.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Davie AP, McMurray JJ. Effect of angiotensin-(1-7) and bradykinin in patients with heart failure treated with an ACE inhibitor. Hypertension. 1999;34(3):457–60.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Wilsdorf T, Gainer JV, Murphey LJ, Vaughan DE, Brown NJ. Angiotensin-(1-7) does not affect vasodilator or TPA responses to bradykinin in human forearm. Hypertension. 2001;37:1136–40.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Sasaki S, Higashi Y, Nakagawa K, Matsuura H, Kajiyama G. OshimaT. Effects of angiotensin-(1-7) on forearm circulation in normotensive subjects and patients with essential hypertension. Hypertension. 2001;38:90–4.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Ueda S, Masumori-Maemoto S, Wada A, Ishii M, Brosnihan KB, Umemura S. Angiotensin(1-7) potentiates bradykinin-induced vasodilatation in man. J Hypertens. 2001;19:2001–9.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Almeida AP, Frábregas BC, Madureira MM, Santos RJ, Campagnole-Santos MJ, Santos RA. Angiotensin-(1-7) potentiates the coronary vasodilatatory effect of bradykinin in the isolated rat heart. Braz J Med Biol Res. 2000;33(6):709–13.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Roks AJ, Nijholt J, van Buiten A, van Gilst WH, de Zeeuw D, Henning RH. Low sodium diet inhibits the local counter-regulator effect of angiotensin-(1-7) on angiotensin II. J Hypertens. 2004;22:2355–61.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Tallant EA, Clark MA. Molecular mechanisms of inhibition of vascular growth by angiotensin-(1-7). Hypertension. 2003;42(4):574–9.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Freeman EJ, Chisolm GM, Ferrario CM, Tallant EA. Angiotensin-(1-7) inhibits vascular smooth muscle cell growth. Hypertension. 1996;28:104–8.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Zhang F, Ren X, Zhao M, Zhou B, Han Y. Angiotensin-(1-7) abrogates angiotensin II-induced proliferation, migration and inflammation in VSMCs through inactivation of ROS-mediated PI3K/Akt and MAPK/ERK signaling pathways. Sci Rep. 2016;6:34621.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Akhtar S, Chandrasekhar B, Attur S, Dhaunsi GS, Yousif MH, Benter IF. Transactivation of ErbB family of receptor tyrosine kinases is inhibited by angiotensin-(1-7) via its Mas receptor. PLoS One. 2015;10(11):e0141657.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Sheng-Long C, Yan-Xin W, Yi-Yi H, Ming F, Jian-Gui H, Yi-Li C, Wen-Jing X, Hong M. AVE0991, a nonpeptide compound, attenuates angiotensin II-induced vascular smooth muscle cell proliferation via induction of Heme Oxygenase-1 and downregulation of p-38 MAPK phosphorylation. Int J Hypertens. 2012;2012:958298.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Tallant EA, Diz DI, Ferrario CM. State-of-the-Art lecture. Antiproliferative actions of angiotensin-(1-7) in vascular smooth muscle. Hypertension. 1999;34(4 Pt 2):950–7.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Langeveld B, van Gilst WH, Tio RA, Zijlstra F, Roks AJ. Angiotensin-(1-7) attenuates neointimal formation after stent implantation in the rat. Hypertension. 2005;45(1):138–41.PubMedCrossRefGoogle Scholar
  40. 40.
    Alsaadon H, Kruzliak P, Smardencas A, Hayes A, Bader M, Angus P, Herath C, Zulli A. Increased aortic intimal proliferation due to MasR deletion in vitro. Int J Exp Pathol. 2015;96(3):183–7.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Yang J, Sun Y, Dong M, Yang X, Meng X, Niu R, Guan J, Zhang Y, Zhang C. Comparison of angiotensin-(1-7), losartan and their combination on atherosclerotic plaque formation in apolipoprotein E knockout mice. Atherosclerosis. 2015;240(2):544–9.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Sui YB, Chang JR, Chen WJ, Zhao L, Zhang BH, Yu YR, et al. Angiotensin-(1-7) inhibits vascular calcification in rats. Peptides. 2013;42:25–34.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    McCollum LT, Gallagher PE, Tallant EA. Angiotensin-(1-7) abrogates mitogen-stimulated proliferation of cardiac fibroblasts. Peptides. 2012;34(2):380–8.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Gallagher PE, Tallant EA. Inhibition of human lung cancer cell growth by angiotensin-(1-7). Carcinogenesis. 2004;25:2045–52.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Ni L, Feng Y, Wan H, Ma Q, Fan L, Qian Y, et al. Angiotensin-(1-7) inhibits the migration and invasion of A549 human lung adenocarcinoma cells through inactivation of the PI3K/Akt and MAPK signaling pathways. Oncol Rep. 2012;27:783–90.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Xu J, Fan J, Wu F, Huang Q, Guo M, Lv Z, Han J, Duan L, Hu G, Chen L, Liao T, Ma W, Tao X, Jin Y. The ACE2/Angiotensin-(1-7)/Mas receptor axis: pleiotropic roles in cancer. Front Physiol. 2017;8:276.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Fraga-Silva RA, Pinheiro SVB, Gonçalves ACC, Alenina N, Bader M, Santos RA. The antithrombotic effect of angiotensin-(1-7) involves Mas-mediated NO release from platelets. Mol Med. 2008;14(1–2):28–35.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Fraga-Silva RA, Costa-Fraga FP, De Sousa FB, Alenina N, Bader M, Sinisterra RD, et al. An orally active formulation of angiotensin-(1-7) produces an antithrombotic effect. Clinics. 2011;66(5):837–41.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Fraga-Silva RA, Da Silva DG, Montecucco F, Mach F, Stergiopulos N, Silva RF, et al. The angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas receptor axis: a potential target for treating thrombotic diseases. Thromb Haemost. 2012;108(6):1089–96.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Fang C, Stavrou E, Schmaier AA, Grobe N, Morris M, Chen A, et al. Angiotensin- (1-7) and Mas decrease thrombosis in Bdkrb2−/− mice by increasing NO and prostacyclin to reduce platelet spreading and glycoprotein VI activation. Blood. 2013;121(15):3023–32.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Mackie AR, Losordo DW. CD34-positive stem cells: in the treatment of heart and vascular disease in human beings. Texas Heart Inst J. 2011;38:474–85.Google Scholar
  52. 52.
    Jarajapu YP, Bhatwadekar AD, Caballero S, Hazra S, Shenoy V, Medina R, Kent D, Stitt AW, Thut C, Finney EM, Raizada MK, Grant MB. Activation of the ACE2/angiotensin-(1-7)/Mas receptor axis enhances the reparative function of dysfunctional diabetic endothelial progenitors. Diabetes. 2013;62(4):1258–69.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Singh N, Joshi S, Guo L, Baker MB, Li Y, Castellano RK, Raizada MK, Jarajapu YP. ACE2/Ang-(1-7)/Mas axis stimulates vascular repair-relevant functions of CD34+ cells. Am J Physiol Heart Circ Physiol. 2015;309(10):H1697–707.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Vasam G, Joshi S, Thatcher SE, Bartelmez SH, Cassis LA, Jarajapu YP. Reversal of bone marrow mobilopathy and enhanced vascular repair by angiotensin-(1-7) in diabetes. Diabetes. 2017;66(2):505–18.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Sampaio WO, Santos RAS, Faria-Silva R, Machado LTM, Schiffrin EL, Touyz RM. Angiotensin-(1-7) through receptor Mas mediates endothelial nitric oxide synthase activation via Akt-dependent pathways. Hypertension. 2007;49:185–92.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Fleming I, Fisslthaler B, Dimmeler S, Kemp BE, Busse R. Phosphorylation of Thr(495) regulates Ca(2+)/calmodulin-dependent endothelial nitric oxide synthase activity. Circ Res. 2001;88:E68–75.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Verano-Braga T, Schwämmle V, Sylvester M, Passos-Silva DG, Peluso AA, Etelvino GM, et al. Time-resolved quantitative phosphoproteomics: new insights into angiotensin-(1-7) signaling networks in human endothelial cells. J Proteome Res. 2012;11(6):3370–81.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Tassone EJ, Sciacqua A, Andreozzi F, Presta I, Perticone M, Carnevale D, Casaburo M, Hribal ML, Sesti G, Perticone F. Angiotensin (1-7) counteracts the negative effect of angiotensin II on insulin signalling in HUVECs. Cardiovasc Res. 2013;99(1):129–36.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Muñoz MC, Giani JF, Burghi V, Mayer MA, Carranza A, Taira CA, Dominici FP. The Mas receptor mediates modulation of insulin signaling by angiotensin-(1-7). Regul Pept. 2012;177(1–3):1–11.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Trachte GJ, Meixner K, Ferrario CM, Khosla MC. Prostaglandin production in response to angiotensin-(1-7) in rabbit isolated vasa deferentia. Prostaglandins. 1990;39(4):385–94.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Jaiswal N, Tallant EA, Diz DI, Khosla MC, Ferrario CM. Subtype 2 angiotensin receptors mediate prostaglandin synthesis in human astrocytes. Hypertension. 1991;17:1115–20.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Jaiswal N, Diz DI, Tallant EA, Khosla MC, Ferrerio CM. Characterization of angiotensin receptors mediating prostaglandin synthesis in CG glioma cells. Am J Phys. 1991;260:R1000–6.CrossRefGoogle Scholar
  63. 63.
    Jaiswal N, Diz DI, Chappell MC, Khosla MC, Ferrario CM. Stimulation of endothelial cell prostaglandin production by angiotensin peptides. Characterization of receptors. Hypertension. 1992;19(2 Suppl):II49–55.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Andreatta-van Leyen S, Romero MF, Khosla MC, Ferrario CM, Douglas JG. Modulation of phospholipase A2 activity and sodium transport by angiotensin-(1-7). Kidney Int. 1993;44:932–6.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Hilchey SD, Bell-Quilley CP. Association between the natriuretic action of angiotensin-(1-7) and selective stimulation of renal prostaglandin I2 release. Hypertension. 1995;25(6):1238–44.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Benter IF, Ferrario CM, Morris M, Diz DI. Antihypertensive actions of angiotensin-(1-7) in spontaneously hypertensive rats. Am J Phys. 1995;269:H313–9.Google Scholar
  67. 67.
    Muthalif MM, Benter IF, Uddin MR, Harper JL, Malik KU. Signal transduction mechanisms involved in angiotensin-(1-7)-stimulated arachidonic acid release and prostanoid synthesis in rabbit aortic smooth muscle cells. J Pharmacol Exp Ther. 1998;284(1):388–98.PubMedPubMedCentralGoogle Scholar
  68. 68.
    Ferreira AJ, Santos RA, Almeida AP. Angiotensin-(1-7) improves the post-ischemic function in isolated perfused rat hearts. Braz J Med Biol Res. 2002;35(9):1083–90.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Oliveira MA, Fortes ZB, Santos RA, Kosla MC, De Carvalho MH. Synergistic effect of angiotensin-(1-7) on bradykinin arteriolar dilation in vivo. Peptides. 1999;20(10):1195–201.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Oliveira MA, Carvalho MH, Nigro D, Passaglia Rde C, Fortes ZB. Elevated glucose blocks angiotensin-(1-7) and bradykinin interaction: the role of cyclooxygenase products. Peptides. 2003;24(3):449–54.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Peña Silva RA, Kung DK, Mitchell IJ, Alenina N, Bader M, Santos RA, Faraci FM, Heistad DD, Hasan DM. Angiotensin 1-7 reduces mortality and rupture of intracranial aneurysms in mice. Hypertension. 2014;64(2):362–8.PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Sampaio WO, Castro CH, Santos RA, Schiffrin EL, Touyz RM. Angiotensin-(1-7) counterregulates angiotensin II signaling in human endothelial cells. Hypertension. 2007;50:1093–8.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Xiao X, Zhang C, Ma X, Miao H, Wang J, Liu L, Chen S, Zeng R, Chen Y, Bihl JC. Angiotensin-(1-7) counteracts angiotensin II-induced dysfunction in cerebral endothelial cells via modulating Nox2/ROS and PI3K/NO pathways. Exp Cell Res. 2015;336(1):58–65.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Carver KA, Smith TL, Gallagher PE, Tallant EA. Angiotensin-(1-7) prevents angiotensin II-induced fibrosis in cremaster microvessels. Microcirculation. 2015;22(1):19–27.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Zhang F, Ren J, Chan K, Chen H. Angiotensin-(1-7) regulates angiotensin II-induced VCAM-1 expression on vascular endothelial cells. Biochem Biophys Res Commun. 2013;430(2):642–6.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Liang B, Wang X, Zhang N, Yang H, Bai R, Liu M, Bian Y, Xiao C, Yang Z. Angiotensin-(1-7) attenuates angiotensin II-induced ICAM-1, VCAM-1, and MCP-1 expression via the MAS receptor through suppression of P38 and NF-κB pathways in HUVECs. Cell Physiol Biochem. 2015;35(6):2472–82.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Xu P, Costa-Goncalves AC, Todiras M, Rabelo LA, Sampaio WO, Moura MM, et al. Endothelial dysfunction and elevated blood pressure in MAS gene-deleted mice. Hypertension. 2008;51:574–80.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Rabelo LA, Xu P, Todiras M, Sampaio WO, Buttgereit J, Bader M, et al. Ablation of angiotensin- (1-7) receptor Mas in C57Bl/6 mice causes endothelial dysfunction. J Am Soc Hypertens. 2008;2:418–24.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Rakušan D, Bürgelová M, Vaněčková I, Vaňourková Z, Husková Z, Skaroupková P, et al. Knockout of angiotensin- (1-7) receptor Mas worsens the course of two-kidney, one-clip Goldblatt hypertension: roles of nitric oxide deficiency and enhanced vascular responsiveness to angiotensin II. Kidney Blood Press Res. 2010;33:476–88.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Faria-Silva R, Duarte FV, Santos RA. Short-term angiotensin(1-7) receptor MAS stimulation improves endothelial function in normotensive rats. Hypertension. 2005;46(4):948–52.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Beyer AM, Guo DF, Rahmouni K. Prolonged treatment with angiotensin 1-7 improves endothelial function in diet-induced obesity. J Hypertens. 2013;31(4):730–8.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Touyz RM, Montezano AC. Angiotensin-(1-7) and vascular function: the clinical context. Hypertension. 2018;71(1):68–9.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.University of ItaúnaBiological Sciences InstituteItaúnaBrazil
  2. 2.Institute of Cardiovascular and Medical SciencesBHF Glasgow Cardiovascular Research Centre, University of GlasgowGlasgowUK

Personalised recommendations