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Pathway Description
Trandolapril Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2013-08-22
Last Updated: 2019-08-29
Trandolapril (trade name: Mavik) belongs to the class of drugs known as angiotensin-converting enzyme (ACE) inhibitors and is used primarily to lower high blood pressure (hypertension). This drug can also be used in the treatment of congestive heart failure and type II diabetes. Trandolapril is a prodrug which, following oral administration, undergoes biotransformation in vivo into its active form trandolaprilat via cleavage of its ester group by the liver. Angiotensin-converting enzyme (ACE) is a component of the body's renin–angiotensin–aldosterone system (RAAS) and cleaves inactive angiotensin I into the active vasoconstrictor angiotensin II. ACE (or kininase II) also degrades the potent vasodilator bradykinin. Consequently, ACE inhibitors decrease angiotensin II concentrations and increase bradykinin concentrations resulting in blood vessel dilation and thereby lowering blood pressure.
References
Trandolapril 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.
Peters, J. ACE inhibitors. In S. Offermanns, & W. Rosenthal (Eds.). Encyclopedic reference of molecular pharmacology (2004) p. 2-5. Berlin, Germany: Springer.
Stanfield, C.L., & Germann, W.J. Principles of human physiology (3rd ed.) (2008). San Francisco, CA: Pearson Education, Inc.;
Wiseman LR, McTavish D: Trandolapril. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in essential hypertension. Drugs. 1994 Jul;48(1):71-90. doi: 10.2165/00003495-199448010-00007.
Pubmed: 7525196
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
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
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
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
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
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