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Pathway Description
Forasartan Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2013-08-22
Last Updated: 2019-08-16
Candesartan (also named Blopress or Atacand) is an active metabolite of angiotensin II receptor blockers (ARBs) pro drug, candesartan cilexetil. Candesartan cilexetil converts to candesartan rapidly in gastrointestinal tract during absorption. Candesartan competes with angiotensin II to bind type-1 angiotensin II receptor (AT1) in many tissues (e.g. vascular smooth muscle, the adrenal glands, etc.) to prevent increasing sodium, water reabsorption and peripheral resistance (that will lead to increasing blood pressure) via aldosterone secretion that is caused by angiotensin II. Therefore, action of candesartan binding to AT1 will result in decreasing blood pressure. For more information on the effects of aldosterone on electrolyte and water excretion, refer to the description of the \spironolactone\:http://pathman.smpdb.ca/pathways/SMP00134/pathway or \triamterene\:http://pathman.smpdb.ca/pathways/SMP00132/pathway pathway, which describes the mechanism of direct aldosterone antagonists. Candesartan is an effective agent for reducing blood pressure and may be used to treat essential hypertension and heart failure.
References
Forasartan Pathway References
Bader, M. Renin-angiotensin-aldosterone system. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (2004) p.810-814. Berlin, Germany: Springer.
[http://www.drugbank.ca](http://www.drugbank.ca/drugs/DB01342)
Stanfield, C.L., & Germann, W.J. Principles of human physiology (3rd ed.) (2008). San Francisco, CA: Pearson Education, Inc.;
Mauzy CA, Hwang O, Egloff AM, Wu LH, Chung FZ: Cloning, expression, and characterization of a gene encoding the human angiotensin II type 1A receptor. Biochem Biophys Res Commun. 1992 Jul 15;186(1):277-84. doi: 10.1016/s0006-291x(05)80804-6.
Pubmed: 1378723
Furuta H, Guo DF, Inagami T: Molecular cloning and sequencing of the gene encoding human angiotensin II type 1 receptor. Biochem Biophys Res Commun. 1992 Feb 28;183(1):8-13. doi: 10.1016/0006-291x(92)91600-u.
Pubmed: 1543512
Bergsma DJ, Ellis C, Kumar C, Nuthulaganti P, Kersten H, Elshourbagy N, Griffin E, Stadel JM, Aiyar N: Cloning and characterization of a human angiotensin II type 1 receptor. Biochem Biophys Res Commun. 1992 Mar 31;183(3):989-95. doi: 10.1016/s0006-291x(05)80288-8.
Pubmed: 1567413
Imai T, Miyazaki H, Hirose S, Hori H, Hayashi T, Kageyama R, Ohkubo H, Nakanishi S, Murakami K: Cloning and sequence analysis of cDNA for human renin precursor. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7405-9. doi: 10.1073/pnas.80.24.7405.
Pubmed: 6324167
Morris BJ: New possibilities for intracellular renin and inactive renin now that the structure of the human renin gene has been elucidated. Clin Sci (Lond). 1986 Oct;71(4):345-55. doi: 10.1042/cs0710345.
Pubmed: 3530608
Hardman JA, Hort YJ, Catanzaro DF, Tellam JT, Baxter JD, Morris BJ, Shine J: Primary structure of the human renin gene. DNA. 1984 Dec;3(6):457-68.
Pubmed: 6391881
Kageyama R, Ohkubo H, Nakanishi S: Primary structure of human preangiotensinogen deduced from the cloned cDNA sequence. Biochemistry. 1984 Jul 31;23(16):3603-9. doi: 10.1021/bi00311a006.
Pubmed: 6089875
Gaillard I, Clauser E, Corvol P: Structure of human angiotensinogen gene. DNA. 1989 Mar;8(2):87-99.
Pubmed: 2924688
Fukamizu A, Takahashi S, Seo MS, Tada M, Tanimoto K, Uehara S, Murakami K: Structure and expression of the human angiotensinogen gene. Identification of a unique and highly active promoter. J Biol Chem. 1990 May 5;265(13):7576-82.
Pubmed: 1692023
Ehlers MR, Riordan JF: Angiotensin-converting enzyme: zinc- and inhibitor-binding stoichiometries of the somatic and testis isozymes. Biochemistry. 1991 Jul 23;30(29):7118-26. doi: 10.1021/bi00243a012.
Pubmed: 1649623
Woodman ZL, Oppong SY, Cook S, Hooper NM, Schwager SL, Brandt WF, Ehlers MR, Sturrock ED: Shedding of somatic angiotensin-converting enzyme (ACE) is inefficient compared with testis ACE despite cleavage at identical stalk sites. Biochem J. 2000 May 1;347 Pt 3:711-8.
Pubmed: 10769174
Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S: A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000 Sep 1;87(5):E1-9. doi: 10.1161/01.res.87.5.e1.
Pubmed: 10969042
Angiotensin Metabolism References
Hussain M, Awan FR: Hypertension regulating angiotensin peptides in the pathobiology of cardiovascular disease. Clin Exp Hypertens. 2018;40(4):344-352. doi: 10.1080/10641963.2017.1377218. Epub 2017 Nov 30.
Pubmed: 29190205
Mori J, Zhang L, Oudit GY, Lopaschuk GD: Impact of the renin-angiotensin system on cardiac energy metabolism in heart failure. J Mol Cell Cardiol. 2013 Oct;63:98-106. doi: 10.1016/j.yjmcc.2013.07.010. Epub 2013 Jul 22.
Pubmed: 23886814
Yim HE, Yoo KH: Renin-Angiotensin system - considerations for hypertension and kidney. Electrolyte Blood Press. 2008 Jun;6(1):42-50. doi: 10.5049/EBP.2008.6.1.42. Epub 2008 Jun 30.
Pubmed: 24459521
Manrique C, Lastra G, Gardner M, Sowers JR: The renin angiotensin aldosterone system in hypertension: roles of insulin resistance and oxidative stress. Med Clin North Am. 2009 May;93(3):569-82. doi: 10.1016/j.mcna.2009.02.014.
Pubmed: 19427492
Mauzy CA, Hwang O, Egloff AM, Wu LH, Chung FZ: Cloning, expression, and characterization of a gene encoding the human angiotensin II type 1A receptor. Biochem Biophys Res Commun. 1992 Jul 15;186(1):277-84. doi: 10.1016/s0006-291x(05)80804-6.
Pubmed: 1378723
Furuta H, Guo DF, Inagami T: Molecular cloning and sequencing of the gene encoding human angiotensin II type 1 receptor. Biochem Biophys Res Commun. 1992 Feb 28;183(1):8-13. doi: 10.1016/0006-291x(92)91600-u.
Pubmed: 1543512
Bergsma DJ, Ellis C, Kumar C, Nuthulaganti P, Kersten H, Elshourbagy N, Griffin E, Stadel JM, Aiyar N: Cloning and characterization of a human angiotensin II type 1 receptor. Biochem Biophys Res Commun. 1992 Mar 31;183(3):989-95. doi: 10.1016/s0006-291x(05)80288-8.
Pubmed: 1567413
Imai T, Miyazaki H, Hirose S, Hori H, Hayashi T, Kageyama R, Ohkubo H, Nakanishi S, Murakami K: Cloning and sequence analysis of cDNA for human renin precursor. Proc Natl Acad Sci U S A. 1983 Dec;80(24):7405-9. doi: 10.1073/pnas.80.24.7405.
Pubmed: 6324167
Morris BJ: New possibilities for intracellular renin and inactive renin now that the structure of the human renin gene has been elucidated. Clin Sci (Lond). 1986 Oct;71(4):345-55. doi: 10.1042/cs0710345.
Pubmed: 3530608
Hardman JA, Hort YJ, Catanzaro DF, Tellam JT, Baxter JD, Morris BJ, Shine J: Primary structure of the human renin gene. DNA. 1984 Dec;3(6):457-68.
Pubmed: 6391881
Kageyama R, Ohkubo H, Nakanishi S: Primary structure of human preangiotensinogen deduced from the cloned cDNA sequence. Biochemistry. 1984 Jul 31;23(16):3603-9. doi: 10.1021/bi00311a006.
Pubmed: 6089875
Gaillard I, Clauser E, Corvol P: Structure of human angiotensinogen gene. DNA. 1989 Mar;8(2):87-99.
Pubmed: 2924688
Fukamizu A, Takahashi S, Seo MS, Tada M, Tanimoto K, Uehara S, Murakami K: Structure and expression of the human angiotensinogen gene. Identification of a unique and highly active promoter. J Biol Chem. 1990 May 5;265(13):7576-82.
Pubmed: 1692023
Ehlers MR, Riordan JF: Angiotensin-converting enzyme: zinc- and inhibitor-binding stoichiometries of the somatic and testis isozymes. Biochemistry. 1991 Jul 23;30(29):7118-26. doi: 10.1021/bi00243a012.
Pubmed: 1649623
Woodman ZL, Oppong SY, Cook S, Hooper NM, Schwager SL, Brandt WF, Ehlers MR, Sturrock ED: Shedding of somatic angiotensin-converting enzyme (ACE) is inefficient compared with testis ACE despite cleavage at identical stalk sites. Biochem J. 2000 May 1;347 Pt 3:711-8.
Pubmed: 10769174
Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S: A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000 Sep 1;87(5):E1-9. doi: 10.1161/01.res.87.5.e1.
Pubmed: 10969042
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