Opportunities for Targeting the Angiotensin-Converting Enzyme 2/Angiotensin-(1-7)/Mas Receptor Pathway in Hypertension

被引:69
作者
Fraga-Silva, Rodrigo Araujo [1 ,4 ]
Ferreira, Anderson Jose [1 ,3 ]
Souza dos Santos, Robson Augusto [1 ,2 ]
机构
[1] Natl Inst Sci & Technol Nanobiopharmaceut, Belo Horizonte, MG, Brazil
[2] Univ Fed Minas Gerais, Dept Fisiol & Biofis, Inst Biol Sci, BR-31270901 Belo Horizonte, MG, Brazil
[3] Univ Fed Minas Gerais, Dept Morphol, Inst Biol Sci, BR-31270901 Belo Horizonte, MG, Brazil
[4] Ecole Polytech Fed Lausanne, Inst Bioengn, Lausanne, Switzerland
关键词
Renin-angiotensin system; RAS; Angiotensin-(1-7); Angiotensin converting enzyme 2; Mas receptor; Hypertension; INSULIN-REGULATED AMINOPEPTIDASE; CARDIOVASCULAR-DISEASE; NITRIC-OXIDE; BIOLOGICAL FUNCTIONS; ENDOTHELIAL-CELLS; NORMOTENSIVE RATS; MIMIC AVE-0991; MAS AGONIST; IN-VIVO; SYSTEM;
D O I
10.1007/s11906-012-0324-1
中图分类号
R6 [外科学];
学科分类号
100210 [外科学];
摘要
It is well known that the renin-angiotensin system (RAS) plays a pivotal role in the pathophysiology of cardiovascular diseases. This is well illustrated by the great success of ACE inhibitors and angiotensin (Ang) II AT(1) blockers in the treatment of hypertension and its complications. In the past decade, the classical concept of RAS orchestrated by a series of enzymatic reactions culminating in the linear generation and action of Ang II has expanded and become more complex. From the discoveries of new components such as the angiotensin converting enzyme 2 and the receptor Mas emerged a novel concept of dual opposite branches of the RAS: one vasoconstrictor and pro-hypertensive composed of ACE/Ang II/AT1; and other vasodilator and anti-hypertensive composed of ACE2/Ang-(1-7)/Mas. In this review we will discuss recent findings concerning the biological role of the ACE2/Ang-(1-7)/Mas arm in the cardiovascular system and highlight the initiatives to develop potential therapeutic strategies based on this axis for treating hypertension.
引用
收藏
页码:31 / 38
页数:8
相关论文
共 84 条
[1]
Evidence that the angiotensin IV (AT4) receptor is the enzyme insulin-regulated aminopeptidase [J].
Albiston, AL ;
McDowall, SG ;
Matsacos, D ;
Sim, P ;
Clune, E ;
Mustafa, T ;
Lee, J ;
Mendelsohn, FAO ;
Simpson, RJ ;
Connolly, LM ;
Chai, SY .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (52) :48623-48626
[2]
Localization and function of angiotensin AT1 receptors [J].
Allen, AM ;
Zhuo, JL ;
Mendelsohn, FAO .
AMERICAN JOURNAL OF HYPERTENSION, 2000, 13 (01) :31S-38S
[3]
Tissue Renin-Angiotensin-Aldosterone Systems: Targets for Pharmacological Therapy [J].
Bader, Michael .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2010, 50 :439-465
[4]
Angiotensin-(1-7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with L-NAME [J].
Benter, IF ;
Yousif, MHM ;
Anim, JT ;
Cojocel, C ;
Diz, DI .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2006, 290 (02) :H684-H691
[5]
The sweeter side of ACE2: Physiological evidence for a role in diabetes [J].
Bindom, Sharell M. ;
Lazartigues, Eric .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2009, 302 (02) :193-202
[6]
Relative affinity of angiotensin peptides and novel ligands at AT1 and AT2 receptors [J].
Bosnyak, Sanja ;
Jones, Emma S. ;
Christopoulos, Arthur ;
Aguilar, Marie-Isabel ;
Thomas, Walter G. ;
Widdop, Robert E. .
CLINICAL SCIENCE, 2011, 121 (7-8) :297-303
[7]
Angiotensin-(1-7) dilates canine coronary arteries through kinins and nitric oxide [J].
Brosnihan, KB ;
Li, P ;
Ferrario, CM .
HYPERTENSION, 1996, 27 (03) :523-528
[8]
Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor [J].
Brunet, A ;
Bonni, A ;
Zigmond, MJ ;
Lin, MZ ;
Juo, P ;
Hu, LS ;
Anderson, MJ ;
Arden, KC ;
Blenis, J ;
Greenberg, ME .
CELL, 1999, 96 (06) :857-868
[9]
Evidence for mas-mediated bradykinin potentiation by the angiotensin-(1-7) nonpeptide mimic AVE 0991 in normotensive rats [J].
Carvalho, Mariana B. L. ;
Duarte, Fernanda V. ;
Faria-Silva, Raphael ;
Fauler, Beatrix ;
Machado, Leonor T. Da Mata ;
de Paula, Renata D. ;
Campagnole-Santos, Maria J. ;
Santos, Robson A. S. .
HYPERTENSION, 2007, 50 (04) :762-767
[10]
Chai SY, 2004, PROTEAS BIOL DIS, P61