Angiotensin (1-7)

Angiotensin (1-7)
Identifiers
Symbol Angiotensin (1-7)
SCOP 2PJ8
SUPERFAMILY 2PJ8

Angiotensin (1-7) (C
41
H
62
N
12
O
11
; Molecular weight = 899.02 g/mol; H-Asp-Arg-Val-Tyr-Ile-His-Pro-OH) is an active heptapeptide of the renin–angiotensin system (RAS). Benter and colleagues showed that Angiotensin (1-7) is a vasodilator agent that plays important roles in cardiovascular organs, such as heart, blood vessels, and kidneys having functions frequently opposed to those attributed to the major effector component of the RAS angiotensin II (Ang II).[1][2]

Synthesis

The polypeptide Ang I can be converted into Ang (1-7) by the actions of neprilysin (NEP)[3] and thimet oligopeptidase (TOP)[4] enzymes. Also, Ang II can be hydrolyzed into Ang (1-7) through the actions of angiotensin-converting enzyme 2 (ACE2). Ang (1-7) binds and activates the G-protein coupled receptor Mas receptor[5] leading to opposite effects of those of Ang II.

Angiotensin (1-7) synthesis pathway

Possible synthesis pathways

Effects of Ang (1-7)

Ang (1-7) has been shown to have anti-oxidant and anti-inflammatory effects.[6][7] Ang (1-7) plays protective roles in cardiomyocytes of spontaneously hypertensive rat by increasing the expression of endothelial and neuronal nitric oxide synthase enzymes leading to augmented production of nitric oxide.[8] Ultimately, Ang (1-7) evokes anti-arrhythmogenic effects in animal models. In blood vessels, Ang (1-7) induces the release of vasodilators such as prostanoids and nitric oxide.

Pharmacological interactions

In addition, it has been demonstrated that Ang (1-7) contributes to the beneficial effects of ACE inhibitors and angiotensin II receptor type 1 antagonists.[9]

References

  1. Schindler C, Bramlage P, Kirch W, Ferrario CM (2007). "Role of the vasodilator peptide angiotensin-(1-7) in cardiovascular drug therapy". Vascular Health and Risk Management. 3 (1): 125–37. PMC 1994039. PMID 17583183.
  2. Benter IF, Ferrario CM, Morris M, Diz DI (July 1995). "Antihypertensive actions of angiotensin-(1-7) in spontaneously hypertensive rats". The American Journal of Physiology. 269 (1 Pt 2): H313–9. doi:10.1152/ajpheart.1995.269.1.H313. PMID 7631863.
  3. Chappell MC (January 2016). "Biochemical evaluation of the renin-angiotensin system: the good, bad, and absolute?". American Journal of Physiology. Heart and Circulatory Physiology. 310 (2): H137–52. doi:10.1152/ajpheart.00618.2015. PMC 4796631. PMID 26475588.
  4. Wilson BA, Nautiyal M, Gwathmey TM, Rose JC, Chappell MC (April 2016). "Evidence for a mitochondrial angiotensin-(1-7) system in the kidney". American Journal of Physiology. Renal Physiology. 310 (7): F637–F645. doi:10.1152/ajprenal.00479.2015. PMC 4824145. PMID 26697984.
  5. Santos RA, Simoes e Silva AC, Maric C, Silva DM, Machado RP, de Buhr I, Heringer-Walther S, Pinheiro SV, Lopes MT, Bader M, Mendes EP, Lemos VS, Campagnole-Santos MJ, Schultheiss HP, Speth R, Walther T (July 2003). "Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas". Proceedings of the National Academy of Sciences of the United States of America. 100 (14): 8258–63. doi:10.1073/pnas.1432869100. PMC 166216. PMID 12829792.
  6. Benter IF, Yousif MH, Dhaunsi GS, Kaur J, Chappell MC, Diz DI (2008). "Angiotensin-(1-7) prevents activation of NADPH oxidase and renal vascular dysfunction in diabetic hypertensive rats". American Journal of Nephrology. 28 (1): 25–33. doi:10.1159/000108758. PMID 17890855.
  7. El-Hashim AZ, Renno WM, Raghupathy R, Abduo HT, Akhtar S, Benter IF (July 2012). "Angiotensin-(1-7) inhibits allergic inflammation, via the MAS1 receptor, through suppression of ERK1/2- and NF-κB-dependent pathways". British Journal of Pharmacology. 166 (6): 1964–76. doi:10.1111/j.1476-5381.2012.01905.x. PMC 3402818. PMID 22339213.
  8. Zisman LS, Meixell GE, Bristow MR, Canver CC (October 2003). "Angiotensin-(1-7) formation in the intact human heart: in vivo dependence on angiotensin II as substrate". Circulation. 108 (14): 1679–81. doi:10.1161/01.CIR.0000094733.61689.D4. PMID 14504185.
  9. Benter IF, Yousif MH, Al-Saleh FM, Raghupathy R, Chappell MC, Diz DI (May 2011). "Angiotensin-(1-7) blockade attenuates captopril- or hydralazine-induced cardiovascular protection in spontaneously hypertensive rats treated with NG-nitro-L-arginine methyl ester". Journal of Cardiovascular Pharmacology. 57 (5): 559–67. doi:10.1097/FJC.0b013e31821324b6. PMC 3095755. PMID 21326110.
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