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Gene Review

Agtr1a  -  angiotensin II receptor, type 1a

Mus musculus

Synonyms: 1810074K20Rik, AG2S, AI551199, AT1, AT1A, ...
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Disease relevance of Agtr1a


Psychiatry related information on Agtr1a

  • We measured light/dark rhythms in BP, heart rate (HR) and drinking behavior in Ang AT1a deficient (AT1a -/-) and wild type (AT1a +/+) mice with arterial telemetric catheters [5].

High impact information on Agtr1a

  • Elevated levels of crosslinked AT1 dimers were present on monocytes of patients with the common atherogenic risk factor hypertension and correlated with an enhanced angiotensin II-dependent monocyte adhesion to endothelial cells [6].
  • In agreement with this finding, factor XIIIA-deficient individuals lacked crosslinked AT1 dimers [6].
  • The type-1 receptor (AT1) mediates the vasopressive and aldosterone-secreting effects of angiotensin II, but the function of the type-2 receptor (AT2) is unknown, although it is expressed in both adult and embryonic life [7].
  • Moreover, the number of infiltrated macrophages was significantly lower in AT1a-/- mice than in WT mice, and double-immunofluorescence staining revealed that these macrophages expressed VEGF protein intensively [8].
  • These effects were not due to reduced systemic blood pressure (SBP), because hydralazine treatment preserved angiogenesis in WT mice although it reduced SBP to a level similar to that of AT1a(-/-) mice [9].

Chemical compound and disease context of Agtr1a


Biological context of Agtr1a


Anatomical context of Agtr1a


Associations of Agtr1a with chemical compounds

  • 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 [1].
  • Agtr1a -/-Agtr1b -/- mice have no systemic pressor response to infusions of angiotensin II, but they respond normally to another vasoconstrictor, epinephrine [15].
  • In the basal state, plasma vasopressin levels are similar in wild-type controls and Agtr1a -/- mice [18].
  • Although urinary sodium excretion was substantially reduced in both groups during the low-salt diet, cumulative sodium balances became negative in Agtr1a-/- mice despite a 6-fold increase in urinary aldosterone [4].
  • The residual constrictor effect observed during AT1 receptor blockade and sensitive to PD 123319 appears to be mediated by a non-AT1 receptor [19].

Physical interactions of Agtr1a

  • We investigated whether GC-A interacts with AT1A signaling in the heart by target deletion and pharmacological blockade or stimulation of AT1A in mice [10].

Regulatory relationships of Agtr1a

  • The carboxyl-terminal cytoplasmic domain of the angiotensin II type 1 (AT1) receptor has recently been shown to interact with several classes of cytoplasmic proteins that regulate different aspects of AT1 receptor physiology [20].
  • METHODS AND RESULTS: We generated double-knockout (KO) mice for GC-A and AT1A by crossing GC-A-KO mice and AT1A-KO mice and blocked AT1 with a selective antagonist, CS-866 [10].
  • Collectively, these findings suggest that Ang II impairs functional hyperemia by activating AT1 receptors and inducing ROS production via a gp91phox containing NADPH oxidase [21].
  • RESULTS: The normal postnatal up-regulation of kininase II was organ-specifically suppressed in Agtr1-/- kidneys at 2 and 3 weeks of age [22].
  • AT1A receptor deficiency-induced reductions in atherosclerosis were independent of systolic blood pressure and measurements of oxidation and chemoattractants [23].

Other interactions of Agtr1a

  • Agtr1a-/-, Agtr1b-/- mice are characterized by normal in utero survival but decreased ex utero survival rate [24].
  • These abnormal phenotypes are quantitatively similar to those found in mutant mice homozygous for the angiotensinogen gene (Agt-/-), indicating that major biological functions of endogenous Ang elucidated by the abnormal phenotypes of Agt-/- are mediated by the AT1 receptors [24].
  • We examined the possibility of whether angiotensin (Ang) II type 1 (AT1) and type 2 (AT2) receptor stimulation differentially regulates collagen production in mouse skin fibroblasts [25].
  • In contrast to wild-type and AT1-/- mice, this treatment led to severe atherosclerotic lesion formation in the aortic sinus and the aorta (oil red O staining) and to an impaired endothelium-dependent vasodilation (organ chamber experiments with isolated aortic segments) in ApoE-/- mice [26].
  • Ang II decreased basal and IGF-I-induced collagen production and inhibited TIMP-1 expression in neonatal skin fibroblasts prepared from AT1a knockout (KO) mice [25].

Analytical, diagnostic and therapeutic context of Agtr1a


  1. 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]
  2. Chimeric mice carrying 'regional' targeted deletion of the angiotensin type 1A receptor gene. Evidence against the role for local angiotensin in the in vivo feedback regulation of renin synthesis in juxtaglomerular cells. Matsusaka, T., Nishimura, H., Utsunomiya, H., Kakuchi, J., Niimura, F., Inagami, T., Fogo, A., Ichikawa, I. J. Clin. Invest. (1996) [Pubmed]
  3. Attenuation of diet-induced weight gain and adiposity through increased energy expenditure in mice lacking angiotensin II type 1a receptor. Kouyama, R., Suganami, T., Nishida, J., Tanaka, M., Toyoda, T., Kiso, M., Chiwata, T., Miyamoto, Y., Yoshimasa, Y., Fukamizu, A., Horiuchi, M., Hirata, Y., Ogawa, Y. Endocrinology (2005) [Pubmed]
  4. Regulation of sodium balance and blood pressure by the AT(1A) receptor for angiotensin II. Oliverio, M.I., Best, C.F., Smithies, O., Coffman, T.M. Hypertension (2000) [Pubmed]
  5. Salt consumption increases blood pressure and abolishes the light/dark rhythm in angiotensin AT1a receptor deficient mice. Chen, Y., Oroszi, T.L., Morris, M. Physiol. Behav. (2006) [Pubmed]
  6. Factor XIIIA transglutaminase crosslinks AT1 receptor dimers of monocytes at the onset of atherosclerosis. AbdAlla, S., Lother, H., Langer, A., el Faramawy, Y., Quitterer, U. Cell (2004) [Pubmed]
  7. Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor in mice. Hein, L., Barsh, G.S., Pratt, R.E., Dzau, V.J., Kobilka, B.K. Nature (1995) [Pubmed]
  8. Role of host angiotensin II type 1 receptor in tumor angiogenesis and growth. Egami, K., Murohara, T., Shimada, T., Sasaki, K., Shintani, S., Sugaya, T., Ishii, M., Akagi, T., Ikeda, H., Matsuishi, T., Imaizumi, T. J. Clin. Invest. (2003) [Pubmed]
  9. Evidence for the importance of angiotensin II type 1 receptor in ischemia-induced angiogenesis. Sasaki, K., Murohara, T., Ikeda, H., Sugaya, T., Shimada, T., Shintani, S., Imaizumi, T. J. Clin. Invest. (2002) [Pubmed]
  10. Guanylyl cyclase-A inhibits angiotensin II type 1A receptor-mediated cardiac remodeling, an endogenous protective mechanism in the heart. Li, Y., Kishimoto, I., Saito, Y., Harada, M., Kuwahara, K., Izumi, T., Takahashi, N., Kawakami, R., Tanimoto, K., Nakagawa, Y., Nakanishi, M., Adachi, Y., Garbers, D.L., Fukamizu, A., Nakao, K. Circulation (2002) [Pubmed]
  11. Pressure overload induces cardiac hypertrophy in angiotensin II type 1A receptor knockout mice. Harada, K., Komuro, I., Shiojima, I., Hayashi, D., Kudoh, S., Mizuno, T., Kijima, K., Matsubara, H., Sugaya, T., Murakami, K., Yazaki, Y. Circulation (1998) [Pubmed]
  12. Essential roles for angiotensin receptor AT1a in bleomycin-induced apoptosis and lung fibrosis in mice. Li, X., Rayford, H., Uhal, B.D. Am. J. Pathol. (2003) [Pubmed]
  13. Telmisartan inhibits both oxidative stress and renal fibrosis after unilateral ureteral obstruction in acatalasemic mice. Sugiyama, H., Kobayashi, M., Wang, D.H., Sunami, R., Maeshima, Y., Yamasaki, Y., Masuoka, N., Kira, S., Makino, H. Nephrol. Dial. Transplant. (2005) [Pubmed]
  14. Enhanced expression of angiotensin II receptor subtypes and angiotensin converting enzyme in medroxyprogesterone-induced mouse mammary adenocarcinomas. Guerra, F.K., Ciuffo, G.M., Elizalde, P.V., Charreau, E.H., Saavedra, J.M. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  15. Reduced growth, abnormal kidney structure, and type 2 (AT2) angiotensin receptor-mediated blood pressure regulation in mice lacking both AT1A and AT1B receptors for angiotensin II. Oliverio, M.I., Kim, H.S., Ito, M., Le, T., Audoly, L., Best, C.F., Hiller, S., Kluckman, K., Maeda, N., Smithies, O., Coffman, T.M. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  16. A novel in vivo mechanism for angiotensin type 1 receptor regulation. Nishimura, H., Matsusaka, T., Fogo, A., Kon, V., Ichikawa, I. Kidney Int. (1997) [Pubmed]
  17. Angiotensin II regulates cellular immune responses through a calcineurin-dependent pathway. Nataraj, C., Oliverio, M.I., Mannon, R.B., Mannon, P.J., Audoly, L.P., Amuchastegui, C.S., Ruiz, P., Smithies, O., Coffman, T.M. J. Clin. Invest. (1999) [Pubmed]
  18. Abnormal water metabolism in mice lacking the type 1A receptor for ANG II. Oliverio, M.I., Delnomdedieu, M., Best, C.F., Li, P., Morris, M., Callahan, M.F., Johnson, G.A., Smithies, O., Coffman, T.M. Am. J. Physiol. Renal Physiol. (2000) [Pubmed]
  19. Renal vascular reactivity in mice: AngII-induced vasoconstriction in AT1A receptor null mice. Ruan, X., Oliverio, M.I., Coffman, T.M., Arendshorst, W.J. J. Am. Soc. Nephrol. (1999) [Pubmed]
  20. Cloning and characterization of ATRAP, a novel protein that interacts with the angiotensin II type 1 receptor. Daviet, L., Lehtonen, J.Y., Tamura, K., Griese, D.P., Horiuchi, M., Dzau, V.J. J. Biol. Chem. (1999) [Pubmed]
  21. Angiotensin II impairs neurovascular coupling in neocortex through NADPH oxidase-derived radicals. Kazama, K., Anrather, J., Zhou, P., Girouard, H., Frys, K., Milner, T.A., Iadecola, C. Circ. Res. (2004) [Pubmed]
  22. Potent antihypertrophic effect of the bradykinin B2 receptor system on the renal vasculature. Tsuchida, S., Miyazaki, Y., Matsusaka, T., Hunley, T.E., Inagami, T., Fogo, A., Ichikawa, I. Kidney Int. (1999) [Pubmed]
  23. Hypercholesterolemia stimulates angiotensin peptide synthesis and contributes to atherosclerosis through the AT1A receptor. Daugherty, A., Rateri, D.L., Lu, H., Inagami, T., Cassis, L.A. Circulation (2004) [Pubmed]
  24. Murine double nullizygotes of the angiotensin type 1A and 1B receptor genes duplicate severe abnormal phenotypes of angiotensinogen nullizygotes. Tsuchida, S., Matsusaka, T., Chen, X., Okubo, S., Niimura, F., Nishimura, H., Fogo, A., Utsunomiya, H., Inagami, T., Ichikawa, I. J. Clin. Invest. (1998) [Pubmed]
  25. Regulation of collagen synthesis in mouse skin fibroblasts by distinct angiotensin II receptor subtypes. Min, L.J., Cui, T.X., Yahata, Y., Yamasaki, K., Shiuchi, T., Liu, H.W., Chen, R., Li, J.M., Okumura, M., Jinno, T., Wu, L., Iwai, M., Nahmias, C., Hashimoto, K., Horiuchi, M. Endocrinology (2004) [Pubmed]
  26. Inhibition of diet-induced atherosclerosis and endothelial dysfunction in apolipoprotein E/angiotensin II type 1A receptor double-knockout mice. Wassmann, S., Czech, T., van Eickels, M., Fleming, I., Böhm, M., Nickenig, G. Circulation (2004) [Pubmed]
  27. Effects of mineralocorticoid receptor gene disruption on the components of the renin-angiotensin system in 8-day-old mice. Hubert, C., Gasc, J.M., Berger, S., Schütz, G., Corvol, P. Mol. Endocrinol. (1999) [Pubmed]
  28. Angiotensin AT1B receptor mediates calcium signaling in vascular smooth muscle cells of AT1A receptor-deficient mice. Zhu, Z., Zhang, S.H., Wagner, C., Kurtz, A., Maeda, N., Coffman, T., Arendshorst, W.J. Hypertension (1998) [Pubmed]
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