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Pathway Description
Lisinopril ACE Inhibitor
Homo sapiens
Drug Action Pathway
Created: 2021-01-12
Last Updated: 2023-10-25
Lisinopril is angiotensin-converting enzyme (ACE) inhibitor for the conversion of angiotensin I into angiotensin II. Angiotensin II is a critical circulating peptide hormone that has powerful vasoconstrictive effects and increases blood pressure. Lisinopril is used to treat hypertension, high blood pressure, congestive heart failure, and chronic renal failure as it decreases blood pressure. Lisinopril is not a prodrug which travels in the blood to inhibit ACE which is from the lungs. Angiotensin has many vasoconstrictive effects by binding to angiotensin II type 1 receptors (AT1) in blood vessels, kidneys, hypothalamus, and posterior pituitary. In blood vessels, AT1 receptors cause vasoconstriction in the tunica media layer of smooth muscle surrounding blood vessels increasing blood pressure. Less angiotensin II that is circulating lowers the constriction of these blood vessels. AT1 receptors in the kidney are responsible for the production of aldosterone which increases salt and water retention which increases blood volume. Less angiotensin II reduces aldosterone production allowing water retention to not increase. AT1 receptors in the hypothalamus are on astrocytes which inhibit the excitatory amino acid transporter 3 from up-taking glutamate back into astrocytes. Glutamate is responsible for the activation of NMDA receptors on paraventricular nucleus neurons (PVN neurons) that lead to thirst sensation. Since angiotensin II levels are lowered, the inhibition of the uptake transporter is not limited decreasing the amount of glutamate activating NMDA on PVN neurons that makes the individual crave drinking less. This lowers the blood volume as well. Lastly, the AT1 receptors on posterior pituitary gland are responsible for the release of vasopressin. Vasopressin is an anti-diuretic hormone that cases water reabsorption in the kidney as well as causing smooth muscle contraction in blood vessels increasing blood pressure. Less angiotensin II activating vasopressin release inhibits blood pressure from increasing. Overall, Lisinopril inhibits the conversion of angiotensin I into angiotensin II, a powerful vasoconstrictor and mediator of high blood pressure so decreasing levels of angiotensin will help reduce blood pressure from climbing in individuals.
References
Lisinopril ACE Inhibitor References
Thomson AH, Kelly JG, Whiting B: Lisinopril population pharmacokinetics in elderly and renal disease patients with hypertension. Br J Clin Pharmacol. 1989 Jan;27(1):57-65. doi: 10.1111/j.1365-2125.1989.tb05335.x.
Pubmed: 2539850
Beermann B: Pharmacokinetics of lisinopril. Am J Med. 1988 Sep 23;85(3B):25-30. doi: 10.1016/0002-9343(88)90346-4.
Pubmed: 2844083
Goa KL, Balfour JA, Zuanetti G: Lisinopril. A review of its pharmacology and clinical efficacy in the early management of acute myocardial infarction. Drugs. 1996 Oct;52(4):564-88. doi: 10.2165/00003495-199652040-00011.
Pubmed: 8891468
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
Salvesen G, Farley D, Shuman J, Przybyla A, Reilly C, Travis J: Molecular cloning of human cathepsin G: structural similarity to mast cell and cytotoxic T lymphocyte proteinases. Biochemistry. 1987 Apr 21;26(8):2289-93. doi: 10.1021/bi00382a032.
Pubmed: 3304423
Hohn PA, Popescu NC, Hanson RD, Salvesen G, Ley TJ: Genomic organization and chromosomal localization of the human cathepsin G gene. J Biol Chem. 1989 Aug 15;264(23):13412-9.
Pubmed: 2569462
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. doi: 10.1101/gr.2596504.
Pubmed: 15489334
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
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
Veenstra-VanderWeele J, Kim SJ, Gonen D, Hanna GL, Leventhal BL, Cook EH Jr: Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early-onset obsessive-compulsive disorder. Mol Psychiatry. 2001 Mar;6(2):160-7. doi: 10.1038/sj.mp.4000806.
Pubmed: 11317217
Myles-Worsley M, Tiobech J, Browning SR, Korn J, Goodman S, Gentile K, Melhem N, Byerley W, Faraone SV, Middleton FA: Deletion at the SLC1A1 glutamate transporter gene co-segregates with schizophrenia and bipolar schizoaffective disorder in a 5-generation family. Am J Med Genet B Neuropsychiatr Genet. 2013 Mar;162B(2):87-95. doi: 10.1002/ajmg.b.32125. Epub 2013 Jan 22.
Pubmed: 23341099
Bailey CG, Ryan RM, Thoeng AD, Ng C, King K, Vanslambrouck JM, Auray-Blais C, Vandenberg RJ, Broer S, Rasko JE: Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. J Clin Invest. 2011 Jan;121(1):446-53. doi: 10.1172/JCI44474. Epub 2010 Dec 1.
Pubmed: 21123949
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
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