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Gene Review

Agt  -  angiotensinogen (serpin peptidase...

Rattus norvegicus

Synonyms: ANRT, Ang, AngII, Angiotensinogen, PAT, ...
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Disease relevance of Agt


Psychiatry related information on Agt

  • Water deprivation for 48 h, leading to extracellular hypertonic hypovolemia with elevated circulating AngII concentrations within the physiological range, caused a significant increase in AoGen-specific hybridization signals in the rostral and medial SFO regions [6].
  • In these cells, the peak response latency was significantly longer to Ang II than to SP (59.5 +/- 4.7 versus 26.5 +/- 2.4 seconds, p less than 0.0001) [7].
  • Central administration of angiotensin IV (Ang IV) analogues attenuates scopolamine-induced amnesia [8].
  • Intracerebroventricular (icv) injection of L-arginine (L-arg), the precursor for NO, has previously been shown to attenuate both dehydration- and angiotensin II (Ang II)-induced drinking behavior [9].

High impact information on Agt


Chemical compound and disease context of Agt


Biological context of Agt


Anatomical context of Agt


Associations of Agt with chemical compounds

  • Stimulation of Ang II receptor increased the intracellular ROS level in a Rac- and p47(phox)-dependent manner [2].
  • Treatment of AT1 receptor-expressing VSMC with AngII resulted in a dose-dependent and time-dependent increase (2- to 4-fold) in (3)H-glucosamine/(35)S-sulfate incorporation, which was abolished by pretreatment with the AT1 receptor antagonist, losartan [21].
  • We administered angiotensin (Ang) II receptor type 1 (AT1) blockade (losartan; 10 or 40 mg/kg per day), type II receptor (AT2) blockades (PD123319; 100 mg/kg per day), or angiotensin-converting enzyme (ACE) inhibitor (enalapril; 30 mg/kg per day) to spontaneously hypertensive rats (SHR) from 10 to 20 weeks of age [22].
  • Studies from our laboratory and others show that oestrogen reduces angiotensin II (Ang II)-induced water intake by ovariectomized rats [23].
  • Ang II receptor-mediated activation of tyrosine phosphatase SHP-1 was assessed by protein tyrosine phosphatase assay [24].

Physical interactions of Agt

  • We examined signaling pathways that are responsible for AngII-induced phosphorylation of CRE-binding protein (CREB) at serine 133 that is a critical marker for the activation in rat vascular smooth muscle cells (VSMC) [25].
  • In contrast, the stimulatory effect of Ang II/III on Na+ transport is more complex and involves PKC and MAPK/ERK pathways [26].
  • Induction of c-Jun gene transcription by Ang II was abolished in PKM, DN-Rac1, and DN-MEKK1, in which Ang II-induced binding of ATF2/c-Jun heterodimer to the activator protein-1 sequence at -190 played a key role [27].
  • Assessment of Ang II receptors by 125I-[Sar1Thr8]-Ang II binding showed that the AT1-receptor subtype predominates in the ganglia [28].
  • These observations suggest locally generated AngII via ATi receptor binding is correlated to TGF-beta1 expression and synthesis at sites of repair and remote sites in the infarcted rat heart [29].

Enzymatic interactions of Agt

  • We also demonstrated that amlodipine or manidipine prevented the Ang II-induced increase in lectin-like oxidized low-density lipoprotein receptor1 (LOX-1) content, thereby restoring control levels [30].
  • Ang II phosphorylated the p44mapk/p42mapk in a time-dependent manner, showing a maximum at 3 minutes [31].
  • However, dynamin was not tyrosine phosphorylated by AngII treatment and seemed to be distinct from the 100 kD phosphotyrosine protein that was found in Nck immunoprecipitates [32].

Regulatory relationships of Agt

  • Ang II-induced nuclear translocation of the green fluorescent protein (GFP)-tagged amino-terminal region of NFAT4 (GFP-NFAT4) was suppressed by p115-RGS or BAPTA but not by diphenyleneiodonium [2].
  • In summary, Ang-(1-7) inhibits Ang II-stimulated MAPK phosphorylation in proximal tubular cells [33].
  • 2. In 9-week-old male anaesthetized LH rats and normotensive (LL) controls pretreated with an angiotensin-converting enzyme inhibitor (quinapril; 10 mg/kg) and an AT1 receptor antagonist (losartan; 10 mg/kg), angiotensin (Ang) II was infused (30 ng/kg per min) to stimulate AT2 receptors [34].
  • 1. The participation of endothelin (ET) in the development and maintenance of hypertension induced by angiotensin (Ang) II was assessed using the non-specific ET receptor antagonist bosentan (30 mg/kg per day) [12].
  • The Ang II-induced activation of SP-1 and AP-1 were significantly suppressed by HS treatment [35].

Other interactions of Agt

  • Ang II-induced NFAT activation was suppressed by diphenyleneiodonium (an NADPH oxidase inhibitor), dominant negative (DN)-Rac, DN-p47(phox), and an inhibitor of Galpha(12/13) (Galpha(12/13)-specific regulator of G protein signaling domain of p115RhoGEF, p115-regulator of G protein signaling (RGS)) [2].
  • It was also shown that SMV, by inhibiting Rac1 activity, reversed Ang II-induced increase in intracellular H2O2 production, Akt activation, and p27 protein expression [17].
  • To determine the Ang receptor status in rat mesenteric vessels, AT1 and AT2 receptor mRNA expression was determined by reverse transcription-polymerase chain reaction [36].
  • Plasma Ang II levels were significantly reduced in DS/H rats compared with DS/L rats, whereas kidney Ang II contents and AT1 receptor protein levels were similar [37].
  • Furthermore, candesartan decreased renal tissue Ang II contents (from 216 +/- 19 to 46 +/- 3 fmol/mL) and ERK1/2, JNK, and BMK1 activities (-45%, -60%, and -70%, respectively) in DS/H rats [37].

Analytical, diagnostic and therapeutic context of Agt


  1. Angiotensin II stimulates c-Jun NH2-terminal kinase in cultured cardiac myocytes of neonatal rats. Kudoh, S., Komuro, I., Mizuno, T., Yamazaki, T., Zou, Y., Shiojima, I., Takekoshi, N., Yazaki, Y. Circ. Res. (1997) [Pubmed]
  2. Galpha12/13-mediated production of reactive oxygen species is critical for angiotensin receptor-induced NFAT activation in cardiac fibroblasts. Fujii, T., Onohara, N., Maruyama, Y., Tanabe, S., Kobayashi, H., Fukutomi, M., Nagamatsu, Y., Nishihara, N., Inoue, R., Sumimoto, H., Shibasaki, F., Nagao, T., Nishida, M., Kurose, H. J. Biol. Chem. (2005) [Pubmed]
  3. Hypertension-induced end-organ damage : A new transgenic approach to an old problem. Luft, F.C., Mervaala, E., Müller, D.N., Gross, V., Schmidt, F., Park, J.K., Schmitz, C., Lippoldt, A., Breu, V., Dechend, R., Dragun, D., Schneider, W., Ganten, D., Haller, H. Hypertension (1999) [Pubmed]
  4. Combined angiotensin and endothelin receptor blockade attenuates adverse cardiac remodeling post-myocardial infarction in the rat: possible role of transforming growth factor beta(1). Tzanidis, A., Lim, S., Hannan, R.D., See, F., Ugoni, A.M., Krum, H. J. Mol. Cell. Cardiol. (2001) [Pubmed]
  5. Endothelin ETA receptor antagonism does not attenuate angiotensin II-induced cardiac hypertrophy in vivo in rats. De Smet, H.R., Menadue, M.F., Oliver, J.R., Phillips, P.A. Clin. Exp. Pharmacol. Physiol. (2003) [Pubmed]
  6. Differential regulation of angiotensinogen and AT1A receptor mRNA within the rat subfornical organ during dehydration. Barth, S.W., Gerstberger, R. Brain Res. Mol. Brain Res. (1999) [Pubmed]
  7. Functional interactions between angiotensin II and substance P in the dorsal medulla. Barnes, K.L., Diz, D.I., Ferrario, C.M. Hypertension (1991) [Pubmed]
  8. Attenuation of scopolamine-induced learning deficits by LVV-hemorphin-7 in rats in the passive avoidance and water maze paradigms. Albiston, A.L., Pederson, E.S., Burns, P., Purcell, B., Wright, J.W., Harding, J.W., Mendelsohn, F.A., Weisinger, R.S., Chai, S.Y. Behav. Brain Res. (2004) [Pubmed]
  9. Effects of L-arginine on angiotensin II-related water and salt intakes. Roth, J.D., Rowland, N.E. Physiol. Behav. (1998) [Pubmed]
  10. Inhibition of diabetic nephropathy by a decoy peptide corresponding to the "handle" region for nonproteolytic activation of prorenin. Ichihara, A., Hayashi, M., Kaneshiro, Y., Suzuki, F., Nakagawa, T., Tada, Y., Koura, Y., Nishiyama, A., Okada, H., Uddin, M.N., Nabi, A.H., Ishida, Y., Inagami, T., Saruta, T. J. Clin. Invest. (2004) [Pubmed]
  11. Statins as antioxidant therapy for preventing cardiac myocyte hypertrophy. Takemoto, M., Node, K., Nakagami, H., Liao, Y., Grimm, M., Takemoto, Y., Kitakaze, M., Liao, J.K. J. Clin. Invest. (2001) [Pubmed]
  12. Endothelin blockade in angiotensin II hypertension: prevention and treatment studies in the rat. Ficai, S., Herizi, A., Mimran, A., Jover, B. Clin. Exp. Pharmacol. Physiol. (2001) [Pubmed]
  13. Fibrosis of atria and great vessels in response to angiotensin II or aldosterone infusion. Sun, Y., Ramires, F.J., Weber, K.T. Cardiovasc. Res. (1997) [Pubmed]
  14. Renal and vascular effects of chronic nitric oxide synthase inhibition: involvement of endothelin 1 and angiotensin II. D'Amours, M., Lebel, M., Grose, J.H., Larivière, R. Can. J. Physiol. Pharmacol. (1999) [Pubmed]
  15. Hyperglycemia activates JAK2 signaling pathway in human failing myocytes via angiotensin II-mediated oxidative stress. Modesti, A., Bertolozzi, I., Gamberi, T., Marchetta, M., Lumachi, C., Coppo, M., Moroni, F., Toscano, T., Lucchese, G., Gensini, G.F., Modesti, P.A. Diabetes (2005) [Pubmed]
  16. GIT1 mediates Src-dependent activation of phospholipase Cgamma by angiotensin II and epidermal growth factor. Haendeler, J., Yin, G., Hojo, Y., Saito, Y., Melaragno, M., Yan, C., Sharma, V.K., Heller, M., Aebersold, R., Berk, B.C. J. Biol. Chem. (2003) [Pubmed]
  17. Simvastatin modulates angiotensin II signaling pathway by preventing Rac1-mediated upregulation of p27. Zeng, L., Xu, H., Chew, T.L., Chisholm, R., Sadeghi, M.M., Kanwar, Y.S., Danesh, F.R. J. Am. Soc. Nephrol. (2004) [Pubmed]
  18. Biochemical properties of the ovarian granulosa cell type 2-angiotensin II receptor. Pucell, A.G., Hodges, J.C., Sen, I., Bumpus, F.M., Husain, A. Endocrinology (1991) [Pubmed]
  19. Angiotensin II induces peroxisome proliferator-activated receptor gamma in PC12W cells via angiotensin type 2 receptor activation. Zhao, Y., Foryst-Ludwig, A., Bruemmer, D., Culman, J., Bader, M., Unger, T., Kintscher, U. J. Neurochem. (2005) [Pubmed]
  20. Cerivastatin prevents angiotensin II-induced renal injury independent of blood pressure- and cholesterol-lowering effects. Park, J.K., Müller, D.N., Mervaala, E.M., Dechend, R., Fiebeler, A., Schmidt, F., Bieringer, M., Schäfer, O., Lindschau, C., Schneider, W., Ganten, D., Luft, F.C., Haller, H. Kidney Int. (2000) [Pubmed]
  21. Regulation of vascular proteoglycan synthesis by angiotensin II type 1 and type 2 receptors. Shimizu-Hirota, R., Sasamura, H., Mifune, M., Nakaya, H., Kuroda, M., Hayashi, M., Saruta, T. J. Am. Soc. Nephrol. (2001) [Pubmed]
  22. Molecular mechanism of angiotensin II type I and type II receptors in cardiac hypertrophy of spontaneously hypertensive rats. Makino, N., Sugano, M., Otsuka, S., Hata, T. Hypertension (1997) [Pubmed]
  23. Oestrogen and weight loss decrease isoproterenol-induced Fos immunoreactivity and angiotensin type 1 mRNA in the subfornical organ of female rats. Krause, E.G., Curtis, K.S., Stincic, T.L., Markle, J.P., Contreras, R.J. J. Physiol. (Lond.) (2006) [Pubmed]
  24. Pivotal role of tyrosine phosphatase SHP-1 in AT2 receptor-mediated apoptosis in rat fetal vascular smooth muscle cell. Cui, T., Nakagami, H., Iwai, M., Takeda, Y., Shiuchi, T., Daviet, L., Nahmias, C., Horiuchi, M. Cardiovasc. Res. (2001) [Pubmed]
  25. Critical role of cAMP-response element-binding protein for angiotensin II-induced hypertrophy of vascular smooth muscle cells. Funakoshi, Y., Ichiki, T., Takeda, K., Tokuno, T., Iino, N., Takeshita, A. J. Biol. Chem. (2002) [Pubmed]
  26. Tyrosine kinase and mitogen-activated protein kinase/extracellularly regulated kinase differentially regulate intracellular calcium concentration responses to angiotensin II/III and bradykinin in rat cortical thick ascending limb. Hus-Citharel, A., Iturrioz, X., Corvol, P., Marchetti, J., Llorens-Cortes, C. Endocrinology (2006) [Pubmed]
  27. Angiotensin II initiates tyrosine kinase Pyk2-dependent signalings leading to activation of Rac1-mediated c-Jun NH2-terminal kinase. Murasawa, S., Matsubara, H., Mori, Y., Masaki, H., Tsutsumi, Y., Shibasaki, Y., Kitabayashi, I., Tanaka, Y., Fujiyama, S., Koyama, Y., Fujiyama, A., Iba, S., Iwasaka, T. J. Biol. Chem. (2000) [Pubmed]
  28. Alterations in sympathetic ganglionic transmission in response to angiotensin II in (mRen2)27 transgenic rats. Aileru, A.A., Logan, E., Callahan, M., Ferrario, C.M., Ganten, D., Diz, D.I. Hypertension (2004) [Pubmed]
  29. Angiotensin II, transforming growth factor-beta1 and repair in the infarcted heart. Sun, Y., Zhang, J.Q., Zhang, J., Ramires, F.J. J. Mol. Cell. Cardiol. (1998) [Pubmed]
  30. Calcium [corrected] channel blockers reduce angiotensin II-induced superoxide generation and inhibit lectin-like oxidized low-density lipoprotein receptor-1 expression in endothelial cells. Toba, H., Shimizu, T., Miki, S., Inoue, R., Yoshimura, A., Tsukamoto, R., Sawai, N., Kobara, M., Nakata, T. Hypertens. Res. (2006) [Pubmed]
  31. Role of mitogen-activated protein kinase in the angiotensin II-induced DNA synthesis in vascular smooth muscle cells. Seewald, S., Seul, C., Kettenhofen, R., Bokemeyer, D., Ko, Y., Vetter, H., Sachinidis, A. Hypertension (1998) [Pubmed]
  32. Identification of Nck interacting proteins in vascular smooth muscle cells. Schmitz, U., Thömmes, K., Beier, I., Düsing, R., Vetter, H. Clin. Exp. Hypertens. (2004) [Pubmed]
  33. Angiotensin-(1-7) inhibits angiotensin II-stimulated phosphorylation of MAP kinases in proximal tubular cells. Su, Z., Zimpelmann, J., Burns, K.D. Kidney Int. (2006) [Pubmed]
  34. Function of renal angiotensin AT2 receptors is not enhanced in Lyon hypertensive rats. Liu, K.L., Lo, M., Benzoni, D., Sassard, J. Clin. Exp. Pharmacol. Physiol. (2003) [Pubmed]
  35. Heat shock treatment suppresses angiotensin II-induced SP-1 and AP-1 and stimulates Oct-1 DNA-binding activity in heart. Chen, Y., Currie, R.W. Inflamm. Res. (2005) [Pubmed]
  36. Role of AT2 receptors in angiotensin II-stimulated contraction of small mesenteric arteries in young SHR. Touyz, R.M., Endemann, D., He, G., Li, J.S., Schiffrin, E.L. Hypertension (1999) [Pubmed]
  37. Effects of AT1 receptor blockade on renal injury and mitogen-activated protein activity in Dahl salt-sensitive rats. Nishiyama, A., Yoshizumi, M., Rahman, M., Kobori, H., Seth, D.M., Miyatake, A., Zhang, G.X., Yao, L., Hitomi, H., Shokoji, T., Kiyomoto, H., Kimura, S., Tamaki, T., Kohno, M., Abe, Y. Kidney Int. (2004) [Pubmed]
  38. Angiotensin II receptor subtype gene expression and cellular localization in the retina and non-neuronal ocular tissues of the rat. Wheeler-Schilling, T.H., Kohler, K., Sautter, M., Guenther, E. Eur. J. Neurosci. (1999) [Pubmed]
  39. Angiotensin II- and IV-induced changes in cerebral blood flow. Roles of AT1, AT2, and AT4 receptor subtypes. Kramár, E.A., Harding, J.W., Wright, J.W. Regul. Pept. (1997) [Pubmed]
  40. Role of AT1 and AT2 receptors in the plasma clearance of angiotensin II. Iyer, S.N., Chappell, M.C., Brosnihan, K.B., Ferrario, C.M. J. Cardiovasc. Pharmacol. (1998) [Pubmed]
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