Novel angiotensin peptides and their physiological implications
DOI:
https://doi.org/10.34019/1982-8047.2019.v45.25929Keywords:
Cardiovascular Physiological Phenomena, Renin-angiotensin System, Angiotensin-peptidesAbstract
Introdution: The renin-angiotensin system (RAS) is the major regulatory system of arterial blood pressure, hydroelectrolytic balance, and body homeostasis. Since the role of the RAS in the cardiovascular function has been described, much of the research in this area has focused on the role of its endocrine axis components, mainly angiotensin II (Ang II), in the cardiovascular and renal physiology. Over the last decades, the findings have shown that the system is much more intricate than thought. Objective: To present, upon a literature review, some of the new elements about the RAS and its physiological implications, updating the reader about the state of the art. Methods Material: Bibliographic review addressing the main PubMed publications related of the novels angiotensin-peptides. Results: Among the novel RAS components, angiotensin–(1-9) is a nonapeptide that exerts antihypertrophy effects in cardiomyocytes, and vasodilatory and anti-hypertensive actions. Angiotensin-(1-7), which differs from Ang II due to the absence of only one aminoacid, is responsible for physiological effects opposite to those of Ang II. Angiotensin A, another biologically active peptide, is synthesized through aspartate decarboxylation, and exerts effects similar to those of Ang II. Alamandine, also formed through decarboxylation, is a heptapeptide showing vasodilatory, antihypertensive, and cardioprotective effects. Conclusion: The discovery of novel angiotensins sheds more light on the view that the RAS is an extensive regulatory system with pathways and alternative axis, much of which without scientific knowledge. Scientific efforts envisioning novel formation pathways of biologically active products may be useful for development of innovative therapeutic strategies and discoveries in the field of several physiological and pathological conditions.
Downloads
References
Hardman JG, Limbird LE, Gilman AG. As bases farmacológicas da terapêutica. 10 ed. Rio de Janeiro: McGraw-Hill; 2005.
Skrbic R, Igic R. Seven decades of angiotensin (1939–2009). Peptides. 2009; 30(10):1945-50. doi: 10.1016/j.peptides.2009.07.003.
Li XC, Zhang J, Zhuo JL. The vasoprotective axes of the renin-angiotensin system: physiological relevance and therapeutic implications in cardiovascular, hypertensive and kidney diseases. Pharmacol Res. 2017; 125(Pt A):21-38.
Danilczk U, Eriksson U, Oudit GY, Penninger JM. Physiological roles of angiotensin-converting enzyme 2. Cell. Mol. Life Sci. 2004; 61(21):2714–9.
Sparks MA, Crowley SD, Gurley SB, Mirotsou M, Coffman TM. Classical Renin-Angiotensin System in Kidney Physiology. Compr Physiol. 2014; 4(3):1201–28.
Snyder RA, Watt KW, Wintroub BU. A human platelet angiotensin I-processing system. Identification of components and inhibition of angiotensin-converting enzyme by product. J. Biol. Chem. 1985; 260(13):7857–60.
Johnson H, Kourtis S, Waters J, Drummer OH. Radioimmunoassay for immunoreactive [des-Leu10]-angiotensin I. Peptides. 1989; 10(3):489–92.
Ocaranza MP, Michea L, Chiong M, Lagos CF, Lavandero S, Jalil JE. Recent insights and therapeutic perspectives of angiotensin-(1-9) in the cardiovascular system. Clin. Sci. Lond. Engl. 2014a; 127(9):549–57.
Flores-Muñoz M, Smith NJ, Haggerty C, Milligan G, Nicklin SA. Angiotensin1-9 antagonises pro-hypertrophic signalling in cardiomyocytes via the angiotensin type 2 receptor. J. Physiol. 2011; 589(Pt. 4):939–51.
Flores-Munoz M, Work LM, Douglas K, Denby L, Dominiczak AF, Graham D, et al. Angiotensin-(1-9) attenuates cardiac fibrosis in the stroke-prone spontaneously hypertensive rat via the angiotensin type 2 receptor. Hypertension. 2012; 59(2):300–7.
Flores-Muñoz M, Godinho BMDC, Almalik A, Nicklin SA. Adenoviral delivery of angiotensin-(1-7) or angiotensin-(1-9) inhibits cardiomyocyte hypertrophy via the mas or angiotensin type 2 receptor. PLoS One. 2012; 7(9):1-6.
Ocaranza MP, Jalil JE. Protective Role of the ACE2/Ang-(1-9) Axis in Cardiovascular Remodeling. Int J Hypertens. 2012; 2012:1-12.
Ocaranza MP, Moya J, Barrientos V, Alzamora R, Hevia D, Morales C, et al. Angiotensin-(1-9) reverses experimental hypertension and cardiovascular damage by inhibition of the angiotensin converting enzyme/Ang II axis. J Hypertens. 2014b; 32(4):771–83.
Jackman HL, Massad MG, Sekosan M, Tan F, Brovkovych V, Marcic BM, et al. Angiotensina 1-9 e 1-7 lançamento no coração humano: o papel da catepsina A. Hipertensão. 2002; 39:976-81.
Lautner RQ, Villela DC, Fraga-Silva RA, Silva N, Verano-Braga T, Costa-Fraga F, et al. Discovery and characterization of alamandine: a novel component of the renin-angiotensin system. Circ Res. 2013; 112(8):1104–11.
Resende GSS. Avaliação dos efeitos cardiovasculares da Angiotensina-(1-9) [Dissertação]. Belo Horizonte (MG): Universidade Federal de Minas Gerais; 2018.
Fattah C, Nather K, McCarroll CS, Hortigon-Vinagre MP, Zamora V, Flores-Munoz M, et al. Gene Therapy With Angiotensin-(1-9) Preserves Left Ventricular Systolic Function After Myocardial Infarction. J Am Coll Cardiol. 2016; 68(24):2652-66.
Santos R, Brosnihan K, Chappell M, Pesquero J, Chernicky C, Greene L, et al. Converting enzyme activity and angiotensin metabolism in the dog brainstem. Hypertension 1988; 11(2 Pt 2):I153.
Santos R, Brum J, Brosnihan K, Ferrario C. The renin-angiotensin system during acute myocardial ischemia in dogs. Hypertension 1990; 15(2 Suppl):I121.
Kohara K, Brosnihan KB, Chappell MC, Khosla MC, Ferrario CM. Angiotensin-(1-7). A member of circulating angiotensin peptides. Hypertension 1991; 17(2):131-8.
Welches WR, Santos R, Chappell MC, Brosnihan KB, Greene LJ, Ferrario CM. Evidence that prolyl endopeptidase participates in the processing of brain angiotensin. J hypertens. 1991; 9(7):631-8.
Santos R, Brosnihan K, Jacobsen D, DiCorleto P, Ferrario C. Production of angiotensin-(1-7) by human vascular endothelium. Hypertension. 1992; 19(2 Suppl):II56.
Smith AI, Turner AJ. What’s new in the renin-angiotensin system? Cell Mol Life Sci. 2004; 61(21):2675–6. doi:10.1007/s00018-004-4319-1.
Ferrario CM, Varagic J. The ANG-(1-7) /ACE2/mas axis in the regulation of nephron function. Am J Physiol Renal Physiol. 2010; 298(6):F1297-305. doi: 10.1152/ajprenal.00110.2010
Andrade AC. Efeito potencializador da Angiotensina (1-7) sobre o aumento da tensão sistólica induzida pelo isoproterenol em corações isolados de ratos [Dissertação]. Belo Horizonte (MG): Universidade Federal de Minas Gerais; 2011.
Zhuo JL, Li XC. New insights and perspectives on intrarenal renin-angiotensin system: focus on intracrine/intracellular angiotensin II. Peptides. 2011; 32(7):1551-65. doi: 10.1016/j.peptides.2011.05.012.
Santos RAS, Sampaio WO, Alzamora AC, Motta-Santos D, Alenina N, Bader M, Campagnole-Santos MJ. The ACE2/angiotensin-(1–7) /MAS axis of the renin-angiotensin system: focus on angiotensin-(1–7). Physiol Rev. 2018; 98(1):505-53. doi: 10.1152/physrev.00023.2016.
Hay M, Polt R, Heien ML, Vanderah TW, Largen-Milnes TM, Rodgers KE, et al. A Novel Angiotensin-(1-7)-glycosylated Mas Receptor Agonist for Treating Vascular Cognitive Impairment and Inflammation Related Memory Dysfunction. J Pharmacol Exp Ther. 2019; 369(1):9-25. doi: 10.1124/jpet.118.254854.
Liu C, Lv XH, Li HX, Cao X, Zhang F, Wang L, et al. Angiotensin-(1-7) suppresses oxidative stress and improves glucose uptake via Mas receptor in adipocytes. Acta Diabetol. 2012; 49(4):291-9. doi: 10.1007/s00592-011-0348-z.
Kittana N. Angiotensin-converting enzyme 2-Angiotensin 1-7/1-9 system: novel promising targets for heart failure treatment. Fundam Clin Pharmacol. 2018; 32(1):14-25. doi: 10.1111/fcp.12318.
Santos RAS, Oudit GY, Verano-Braga T, Canta G, Steckelings UM, Bader M. The Renin-Angiotensin system: going beyond the classical paradigms. Am J Physiol Heart Circ Physiol. 2019; 316(5): H958-H970. doi:10.1152/ajpheart.00723.2018
Karnik SS, Unal H, Kemp JR, Tirupula KC, Eguchi S, Vanderheyden PM, et al. International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli. Pharmacol Rev. 2015; 67(4):754-819. doi: 10.1124/pr.114.010454.
Skrbic R, Igic R. Seven decades of angiotensin (1939–2009). Peptides. 2009; 30(10):1945-50. doi: 10.1016/j.peptides.2009.07.003
Brunton LL, Chabner BA, Knollmann BC. As Bases Farmacológicas da Terapêutica de Goodman & Gilman. 12 ed. Rio de Janeiro: McGraw-Hill;2012.
Soares ER, Barbosa CM, Campagnole-Santos MJ, Santos RAS, Alzamora AC. Hypotensive effect induced by microinjection of Alamandine, a derivative of angiotensin-(1–7), into caudal ventrolateral medulla of 2K1C hypertensive rats. Peptides. 2017; 96:67-75. doi: 10.1016/j.peptides.2017.09.005
Machado-Silva A, Passos-Silva D, Santos RA, Sinisterra RD. Therapeutic uses for Angiotensin-(1-7). Expert Opin Ther Pat. 2016; 26(6):669-78. doi: 10.1080/13543776.2016.1179283.
Jankowski V, Vanholder R, van der Giet M, et al. Mass-spectrometric identification of a novel angiotensin peptide in human plasma. Arterioscler Thromb Vasc Biol. 2007; 27(2):297–302.
De La Serna, F. Novedades en el sistema renina-angiotensina. Insuf card. 2014; 9(1):16-24.
Jaraslov H, Ludovit P, Fedor S. Angiotensin A/Alamandine/MrgD Axis: Another Clue to Understanding Cardiovascular Pathophysiology. Int J Mol Sci. 2016; 17(7):1-9.
Casare FAM. Efeitos da interação da Angiotensina II e o receptor AT1 ou Endotelina 3 e os receptores ETA e ETB e na morfologia renal de ratos [Tese]. São Paulo (SP): Universidade de São Paulo; 2015.
Jesus ICG, Scalzo S, Alves F, Marques K, Rocha-Resende C, Bader M, et al. Alamandine acts via MrgD to induce AMPK/NO activation against ANG II hypertrophy in cardiomyocytes. Am J Physiol Cell Physiol. 2018 ;314(6):C702-11.
Qaradakhi T, Apostolopoulos V, Zulli A. Angiotensin (1-7) and Alamandine: Similarities and differences. Pharmacol Res. 2016; 111:820-6. doi: 10.1016/j.phrs.2016.07.025.
Silva AR, Lenglet S, Carbone F, Burger F, Roth A, Liberale L, et al. Alamandine abrogates neutrophil degranulation in atherosclerotic mice. Eur J Clin Invest. 2017; 47(2):117-28. doi: 10.1111/eci.12708.
Qaradakhi T, Matsoukas MT, Hayes A, Rybalka E, Caprnda M, Rimarova K, et al. Alamandine reverses hyperhomocysteinemia-induced vascular dysfunction via PKA-dependent mechanisms. Cardiovasc Ther. 2017; 35(6):1-11. doi: 10.1111/1755-5922.12306.
Liu C, Yang CX, Chen XR, Liu BX, Li Y, Wang XZ, et al. Alamandine attenuates hypertension and cardiac hypertrophy in hypertensive rats. Amino Acids. 2018; 50(8):1071-81. doi: 10.1007/s00726-018-2583-x.
Moraes PL, Kangussu LM, Silva Jr. LG, Castro CH, Santos RAS, Ferreira AJ. Cardiovascular effects of small peptides of the renin angiotensin system. Physiol Rep. 2017; 5(22):1-7. doi:/10.14814/phy2.13505.
Mirabito Colafella KM, Bovée DM, Danser AHJ. The renin angiotensin aldosterone system and its therapeutic targets. Exp Eye Res. 2019; 186.107680. doi:https://doi.org/10.1016/j.exer.2019.05.020.
Skiba DS, Nosalski R, Mikolajczyk TP, Siedlinski M, Rios FJ, Montezano AC et al. Anti-atherosclerotic effect of the angiotensin 1–7 mimetic AVE0991 is mediated by inhibition of perivascular and plaque inflammation in early atherosclerosis. Br J Pharmacol. 2017; 174(22):4055–69. doi: 10.1111/bph.13685.
Simões e Silva AC, Silveira KD, Ferreira AJ, Teixeira MM. ACE2, angiotensin-(1-7) and Mas receptor axis in inflammation and fibrosis. Br J Pharmacol. 2013; 169(3):477–92. doi: 10.1111/bph.12159.
Tan WSD, Liao W, Zhou S, Mei D, Wong WF. Targeting the renin–angiotensin system as novel therapeutic strategy for pulmonary diseases. Curr Opin Pharmacol. 2018; 40:9-17. doi: 10.3389/fphys.2017.00276.
Xu J, Fan J, Wu F, Qi H, Mengfei Guo, Lv Z et al. The ACE2/Angiotensin-(1–7)/Mas Receptor Axis: Pleiotropic Roles in Cancer. Front Physiol. 2017; 8:276. doi: 10.3389/fphys.2017.00276.
Additional Files
Published
How to Cite
Issue
Section
License
Cessão de Primeira Publicação à HU Revista
Os autores mantém todos os direitos autorais sobre a publicação, sem restrições, e concedem à HU Revista o direito de primeira publicação, com o trabalho licenciado sob a Licença Creative Commons Attribution que permite o compartilhamento irrestrito do trabalho, com reconhecimento da autoria e crédito pela citação de publicação inicial nesta revista, referenciando inclusive seu DOI.
