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Chemical Compound Review

Angiotensin     (3S)-3-amino-3-[[(1S)-1- [[(1S)-1-[[(1S)-1...

Synonyms: Angiotensin 2, ANGIOTENSIN II, Delivert (TN), CHEMBL408403, Ang II, ...
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Disease relevance of ANGIOTENSIN II

  • A growing body of evidence supports the notion that angiotensin II (Ang II), the central product of the renin-angiotensin system, may play a central role not only in the etiology of hypertension but also in the pathophysiology of cardiovascular and renal diseases in humans [1].
  • The Ang II effect on hypertrophy was shown not to result from stimulation of the endogenous renin-angiotensis system [2].
  • No significant levels of fibrosis, mitotic growth, or cytokine infiltration were detected in Ang II-treated mice [2].
  • However, the role of FGF-2 in Ang II-induced cardiac hypertrophy has not been established [3].
  • Ang II stimulation of quiescent cells in which p27(Kip1) levels are high results in hypertrophy but promotes hyperplasia when levels of p27(Kip1) are low, as in the presence of other growth factors [4].

Psychiatry related information on ANGIOTENSIN II


High impact information on ANGIOTENSIN II

  • Furthermore, in vivo recent evidence suggest that the activation of mitogen-activated protein kinases and activator protein-1 by Ang II may play the key role in cardiovascular and renal diseases [1].
  • In this review, we focus on the role of Ang II in cardiovascular and renal diseases at the molecular and cellular levels and discuss up-to-date evidence concerning the in vitro and in vivo actions of Ang II and the pharmacological effects of angiotensin receptor antagonists in comparison with angiotensin-converting enzyme inhibitors [1].
  • Although AT(1) receptors mediate most of the known actions of Ang II, the AT(2) receptor contributes to the regulation of blood pressure and renal function [10].
  • The identification of the presence of prorenin, renin, angiotensinogen, angiotensin-converting enzyme, angiotensin II (Ang II), and Ang II receptors in the ovary suggests that there is a functional ovarian renin-angiotensin system (RAS) [11].
  • Ang II modulates ovarian steroidogenesis and formation of the corpus luteum and also stimulates oocyte maturation and ovulation via Ang II receptors on granulosa cells [11].

Chemical compound and disease context of ANGIOTENSIN II


Biological context of ANGIOTENSIN II


Anatomical context of ANGIOTENSIN II


Associations of ANGIOTENSIN II with other chemical compounds

  • Administration of losartan alone to block endogenous Ang II shifted the baroreflex curve to the left as indicated by a decrease in BP50 from 71.2 +/- 2.7 to 64.7 +/- 2.5 mmHg (P < 0.05) [24].
  • Ang II receptor activation increases cytosolic Ca(2+) levels to enhance the synthesis and secretion of aldosterone, a recently identified early pathogenic stimulus that adversely influences cardiovascular homeostasis [18].
  • Local generation of cardiac Ang II from mast cell-derived renin also elicited norepinephrine release from isolated sympathetic nerve terminals [25].
  • Binding of 125I Ang II to renal cortical basolateral membranes of captopril-treated rabbits decreased from 2.9 +/- 0.55 to 1.4 +/- 0.17 fmol/mg protein (n = 6; P < 0.025) [19].
  • AT(2)-null mice had higher renal interstitial fluid (RIF) 6-keto-PGF(1alpha) (a stable hydrolysis product of prostacyclin [PGI(2)]) and PGE(2) levels than did WT mice, and had similar increases in PGE(2) and 6-keto-PGF(1alpha) in response to dietary sodium restriction and Ang II infusion [26].

Gene context of ANGIOTENSIN II

  • Little is known about the in vivo contribution of AT1 and AT2 receptor activation to the biological action of Ang II [12].
  • When control chimeric mice made of wild-type cells and ROSA26 cells (i.e., both carrying intact Agtr1a) were infused with Ang II, fibroblast proliferation was found equally in these cardiomyocyte types [21].
  • Ang II infusion also reduced medullary blood flow in COX2-deficient but not in control or COX1-deficient animals, suggesting synthesis of COX2-dependent vasodilators in the renal medulla [27].
  • ApoE-/- mice transplanted with bone marrow derived from ApoE-/-OPN-/- mice had less Ang II-induced atherosclerosis compared with animals receiving ApoE-/-OPN+/+ cells [28].
  • These data suggest an important role for leukocyte-derived OPN in mediating Ang II-accelerated atherosclerosis and aneurysm formation [28].

Analytical, diagnostic and therapeutic context of ANGIOTENSIN II


  1. Molecular and cellular mechanisms of angiotensin II-mediated cardiovascular and renal diseases. Kim, S., Iwao, H. Pharmacol. Rev. (2000) [Pubmed]
  2. TGF-beta1 mediates the hypertrophic cardiomyocyte growth induced by angiotensin II. Schultz, J.e.l. .J., Witt, S.A., Glascock, B.J., Nieman, M.L., Reiser, P.J., Nix, S.L., Kimball, T.R., Doetschman, T. J. Clin. Invest. (2002) [Pubmed]
  3. Dilated cardiomyopathy and impaired cardiac hypertrophic response to angiotensin II in mice lacking FGF-2. Pellieux, C., Foletti, A., Peduto, G., Aubert, J.F., Nussberger, J., Beermann, F., Brunner, H.R., Pedrazzini, T. J. Clin. Invest. (2001) [Pubmed]
  4. A novel role for the cyclin-dependent kinase inhibitor p27(Kip1) in angiotensin II-stimulated vascular smooth muscle cell hypertrophy. Braun-Dullaeus, R.C., Mann, M.J., Ziegler, A., von der Leyen, H.E., Dzau, V.J. J. Clin. Invest. (1999) [Pubmed]
  5. Response of proximal tubules to angiotensin II changes during maturation. Garvin, J.L., Beierwaltes, W.H. Hypertension (1998) [Pubmed]
  6. Tissue angiotensin II as a modulator of erectile function. I. Angiotensin peptide content, secretion and effects in the corpus cavernosum. Kifor, I., Williams, G.H., Vickers, M.A., Sullivan, M.P., Jodbert, P., Dluhy, R.G. J. Urol. (1997) [Pubmed]
  7. Angiotensin II interacts with prostaglandin F2alpha and endothelin-1 as a local luteolytic factor in the bovine corpus luteum in vitro. Hayashi, K., Miyamoto, A. Biol. Reprod. (1999) [Pubmed]
  8. Characterization of receptors for angiotensin-induced drinking and blood pressure responses in conscious rats using angiotensin analogs extended at the N-terminal. Kawabe, H., Husain, A., Khosla, M.C., Smeby, R.R., Bumpus, F.M., Ferrario, C.M. Neuroendocrinology (1986) [Pubmed]
  9. AT(2) but not AT(1) receptor antagonism abolishes angiotensin II increase of the acquisition of conditioned avoidance responses in rats. Braszko, J.J. Behav. Brain Res. (2002) [Pubmed]
  10. International union of pharmacology. XXIII. The angiotensin II receptors. de Gasparo, M., Catt, K.J., Inagami, T., Wright, J.W., Unger, T. Pharmacol. Rev. (2000) [Pubmed]
  11. The ovarian renin-angiotensin system in reproductive physiology. Yoshimura, Y. Frontiers in neuroendocrinology. (1997) [Pubmed]
  12. Chronic blockade of AT2-subtype receptors prevents the effect of angiotensin II on the rat vascular structure. Levy, B.I., Benessiano, J., Henrion, D., Caputo, L., Heymes, C., Duriez, M., Poitevin, P., Samuel, J.L. J. Clin. Invest. (1996) [Pubmed]
  13. Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice. Daugherty, A., Manning, M.W., Cassis, L.A. J. Clin. Invest. (2000) [Pubmed]
  14. A central role of EGF receptor transactivation in angiotensin II -induced cardiac hypertrophy. Shah, B.H., Catt, K.J. Trends Pharmacol. Sci. (2003) [Pubmed]
  15. Differential effects of angiotensin II on cardiac cell proliferation and intramyocardial perivascular fibrosis in vivo. McEwan, P.E., Gray, G.A., Sherry, L., Webb, D.J., Kenyon, C.J. Circulation (1998) [Pubmed]
  16. Angiotensin II receptor antagonist TCV-116 induces regression of hypertensive left ventricular hypertrophy in vivo and inhibits the intracellular signaling pathway of stretch-mediated cardiomyocyte hypertrophy in vitro. Kojima, M., Shiojima, I., Yamazaki, T., Komuro, I., Zou, Z., Wang, Y., Mizuno, T., Ueki, K., Tobe, K., Kadowaki, T. Circulation (1994) [Pubmed]
  17. Involvement of the area postrema in the regulation of sympathetic outflow to the cardiovascular system. Bishop, V.S., Hay, M. Frontiers in neuroendocrinology. (1993) [Pubmed]
  18. Molecular basis for the modulation of native T-type Ca channels in vivo by Ca /calmodulin-dependent protein kinase II. Yao, J., Davies, L.A., Howard, J.D., Adney, S.K., Welsby, P.J., Howell, N., Carey, R.M., Colbran, R.J., Barrett, P.Q. J. Clin. Invest. (2006) [Pubmed]
  19. Angiotensin II upregulates type-1 angiotensin II receptors in renal proximal tubule. Cheng, H.F., Becker, B.N., Burns, K.D., Harris, R.C. J. Clin. Invest. (1995) [Pubmed]
  20. Vascular smooth muscle cell hypertrophy vs. hyperplasia. Autocrine transforming growth factor-beta 1 expression determines growth response to angiotensin II. Gibbons, G.H., Pratt, R.E., Dzau, V.J. J. Clin. Invest. (1992) [Pubmed]
  21. Communication between myocytes and fibroblasts in cardiac remodeling in angiotensin chimeric mice. Matsusaka, T., Katori, H., Inagami, T., Fogo, A., Ichikawa, I. J. Clin. Invest. (1999) [Pubmed]
  22. Induction of platelet-derived growth factor A-chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells. Naftilan, A.J., Pratt, R.E., Dzau, V.J. J. Clin. Invest. (1989) [Pubmed]
  23. Cardiac-specific overexpression of AT1 receptor mutant lacking G alpha q/G alpha i coupling causes hypertrophy and bradycardia in transgenic mice. Zhai, P., Yamamoto, M., Galeotti, J., Liu, J., Masurekar, M., Thaisz, J., Irie, K., Holle, E., Yu, X., Kupershmidt, S., Roden, D.M., Wagner, T., Yatani, A., Vatner, D.E., Vatner, S.F., Sadoshima, J. J. Clin. Invest. (2005) [Pubmed]
  24. Role of AT1 receptors in the resetting of the baroreflex control of heart rate by angiotensin II in the rabbit. Wong, J., Chou, L., Reid, I.A. J. Clin. Invest. (1993) [Pubmed]
  25. Cardiac mast cell-derived renin promotes local angiotensin formation, norepinephrine release, and arrhythmias in ischemia/reperfusion. Mackins, C.J., Kano, S., Seyedi, N., Schäfer, U., Reid, A.C., Machida, T., Silver, R.B., Levi, R. J. Clin. Invest. (2006) [Pubmed]
  26. Increased renal vasodilator prostanoids prevent hypertension in mice lacking the angiotensin subtype-2 receptor. Siragy, H.M., Senbonmatsu, T., Ichiki, T., Inagami, T., Carey, R.M. J. Clin. Invest. (1999) [Pubmed]
  27. Opposite effects of cyclooxygenase-1 and -2 activity on the pressor response to angiotensin II. Qi, Z., Hao, C.M., Langenbach, R.I., Breyer, R.M., Redha, R., Morrow, J.D., Breyer, M.D. J. Clin. Invest. (2002) [Pubmed]
  28. Angiotensin II-accelerated atherosclerosis and aneurysm formation is attenuated in osteopontin-deficient mice. Bruemmer, D., Collins, A.R., Noh, G., Wang, W., Territo, M., Arias-Magallona, S., Fishbein, M.C., Blaschke, F., Kintscher, U., Graf, K., Law, R.E., Hsueh, W.A. J. Clin. Invest. (2003) [Pubmed]
  29. Endothelium-derived relaxing factor/nitric oxide modulates angiotensin II action in the isolated microperfused rabbit afferent but not efferent arteriole. Ito, S., Arima, S., Ren, Y.L., Juncos, L.A., Carretero, O.A. J. Clin. Invest. (1993) [Pubmed]
  30. Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation. Tsutsumi, Y., Matsubara, H., Masaki, H., Kurihara, H., Murasawa, S., Takai, S., Miyazaki, M., Nozawa, Y., Ozono, R., Nakagawa, K., Miwa, T., Kawada, N., Mori, Y., Shibasaki, Y., Tanaka, Y., Fujiyama, S., Koyama, Y., Fujiyama, A., Takahashi, H., Iwasaka, T. J. Clin. Invest. (1999) [Pubmed]
  31. An unexpected role for angiotensin II in the link between dietary salt and proximal reabsorption. Thomson, S.C., Deng, A., Wead, L., Richter, K., Blantz, R.C., Vallon, V. J. Clin. Invest. (2006) [Pubmed]
  32. Study of the rat adrenal renin-angiotensin system at a cellular level. Chiou, C.Y., Williams, G.H., Kifor, I. J. Clin. Invest. (1995) [Pubmed]
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