Ramipril Increases Adma Concentration in Acute Myocardial Infarction in Rats Induced by Isoproterenol


  • Gestina Aliska Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Andalas, West Sumatra, Indonesia https://orcid.org/0000-0002-3234-898X
  • Alief Dhuha Department of Anatomy, Faculty of Medicine, Universitas Abdurrab, Pekanbaru, Riau, Indonesia https://orcid.org/0000-0002-4948-892X
  • Rahmatini Rahmatini Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Andalas, West Sumatra, Indonesia
  • Rita Hamdani Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Andalas, West Sumatra, Indonesia
  • Nita Afriani Department of Histology
  • Tofrizal Tofrizal Department of Anatomical Pathology, Faculty of Medicine, Universitas Andalas, West Sumatra, Indonesia
  • Hirowati Ali Department of Biochemistry, Faculty of Medicine, Universitas Andalas, West Sumatra, Indonesia
  • Nisa Pratiwi Medical Doctor Programme, Faculty of Medicine, Universitas Andalas, West Sumatra, Indonesia
  • Vinta Nuranisyah Medical Doctor Programme, Faculty of Medicine, Universitas Andalas, West Sumatra, Indonesia
  • Liganda Endo Mahata Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Andalas, West Sumatra, Indonesia https://orcid.org/0000-0002-3856-9003
  • Dedy Kurnia Department of Anesthesiology and Intensive Therapy, Faculty of Medicine, Universitas Andalas, West Sumatra, Indonesia




Asymmetric dimethylarginine, Dimethylarginine dimethylaminohydrolase, Nitric oxide, Myocardial infarction, Ramipril


In experimental animals, the induction of isoproterenol which is a synthetic of catecholamine, can cause acute myocardial infarction where the pathophysiology and morphology are the same as myocardial infarction in humans. Isoproterenol induction will increase oxidative stress, which will damage the enzyme dimethylarginine dimethylaminohydrolase (DDAH), thus causing asymmetric dimethylarginine (ADMA) levels to increase in circulation. Increased levels of ADMA will inhibit the activity of the enzyme nitric oxide synthase, which results in decreased nitric oxide resulting in endothelial damage. This study aims to determine the effect of Ramipril on asymmetric dimethylarginine (ADMA) levels in rats (Rattus norvegicus) Wistar strain with acute myocardial infarction.

Eighteen male Wistar rats (150-250 g) were randomly allocated into three groups: negative control group, positive control, and treatment group. The treatment group was pretreated with Ramipril at dose 3 mg/kg BW orally for seven days. Acute myocardial infarction was induced in positive control groups and treatment groups by subcutaneous injection of isoproterenol (85 mg/kg BW) for two consecutive days. Twenty-four hours after the last administration, rats from all groups were anesthetized and sacrificed for blood sample collection to evaluate the level of Asymmetric Dimethylarginine with Enzym-linked Immunosorbent Assay (ELISA) method. The result showed that ADMA levels were increased in the treatment group after pretreated with Ramipril. This study concluded that pretreatment with Ramipril increased ADMA concentration in acute myocardial infarction rats induced by isoproterenol.


Download data is not yet available.


Metrics Loading ...

Plum Analytics Artifact Widget Block


Li H, Xie YH, Yang Q, Wang SW, Zhang BL, Wang JB, et al. Cardioprotective effect of paeonol and danshensu combination on isoproterenol-induced myocardial injury in rats. PLoS One. 2012;7(11):e48872. https://doi.org/10.1371/journal.pone.0048872 PMid:23139821 DOI: https://doi.org/10.1371/journal.pone.0048872

Higashi Y, Maruhashi T, Noma K, Kihara Y. Oxidative stress and endothelial dysfunction: Clinical evidence and therapeutic implications. Trends Cardiovasc Med. 2014;24(4):165-9. https://doi.org/10.1016/j.tcm.2013.12.001 PMid:24373981 DOI: https://doi.org/10.1016/j.tcm.2013.12.001

Su JB. Vascular endothelial dysfunction and pharmacological treatment. World J Cardiol. 2015;7(11):719-41. https://doi.org/10.1016/s0008-6363(02)00617-x PMid:26635921 DOI: https://doi.org/10.4330/wjc.v7.i11.719

Sydow K, Schwedhelm E, Arakawa N, Bode-Böger SM, Tsikas D, Hornig B, et al. ADMA and oxidative stress are responsible for endothelial dysfunction in hyperhomocyst(e)inemia: Effects of L-arginine and B Vitamins. Cardiovasc Res. 2003;57(1):244-52. PMid:12504835 DOI: https://doi.org/10.1016/S0008-6363(02)00617-X

Steyers CM 3rd, Miller FJ Jr. Endothelial dysfunction in chronic inflammatory diseases. Int J Mol Sci. 2014;15(7):11324-49. https://doi.org/10.3390/ijms150711324 PMid:24968272 DOI: https://doi.org/10.3390/ijms150711324

Her AY, Choi BG, Rha SW, Kim YH, Choi CU, Jeong MH. The impact of angiotensin-converting-enzyme inhibitors versus angiotensin receptor blockers on 3-year clinical outcomes in patients with acute myocardial infarction without hypertension. PLoS One. 2020;15(11):e0242314. https://doi.org/10.1371/journal.pone.0242314 PMid:33253206 DOI: https://doi.org/10.1371/journal.pone.0242314

Erdös EG, Tan F, Skidgel RA. Angiotensin I-converting enzyme inhibitors are allosteric enhancers of kinin B1 and B2 receptor function. Hypertension. 2010;55(2):214-20. https://doi.org/10.1161/hypertensionaha.109.144600 PMid:20065150 DOI: https://doi.org/10.1161/HYPERTENSIONAHA.109.144600

Chen JW, Hsu NW, Wu TC, Lin SJ, Chang MS. Long-term angiotensin-converting enzyme inhibition reduces plasma asymmetric dimethylarginine and improves endothelial nitric oxide bioavailability and coronary microvascular function in patients with syndrome X. Am J Cardiol. 2002;90(9):974-82. https://doi.org/10.1016/s0002-9149(02)02664-4 PMid:12398965 DOI: https://doi.org/10.1016/S0002-9149(02)02664-4

Allawadhi P, Khurana A, Sayed N, Kumari P, Godugu C. Isoproterenol-induced cardiac ischemia and fibrosis: Plant-based approaches for intervention. Phytother Res. 2018;32(10):1908-32. https://doi.org/10.1002/ptr.6152 PMid:30009418 DOI: https://doi.org/10.1002/ptr.6152

Iqbal R, Akhtar MS, Hassan MQ, Jairajpuri Z, Akhtar M, Najmi AK. Pitavastatin ameliorates myocardial damage by preventing inflammation and collagen deposition via reduced free radical generation in isoproterenol-induced cardiomyopathy. Clin Exp Hypertens. 2019;41(5):434-43. https://doi.org/10.1080/10641963.2018.1501059 PMid:30192645 DOI: https://doi.org/10.1080/10641963.2018.1501059

Sampath PD, Kannan V. Mitigation of mitochondrial dysfunction and regulation of eNOS expression during experimental myocardial necrosis by alpha-mangostin, a xanthonic derivative from Garcinia mangostana. Drug Chem Toxicol. 2009;32(4):344- 52. https://doi.org/10.1080/01480540903159210 PMid:19793027 DOI: https://doi.org/10.1080/01480540903159210

Yu X, Ge L, Niu L, Lian X, Ma H, Pang L. The dual role of inducible nitric oxide synthase in myocardial ischemia/reperfusion injury: Friend or foe? Oxid Med Cell Longev. 2018;2018:8364848. https://doi.org/10.1155/2018/8364848 PMid:30510628 DOI: https://doi.org/10.1155/2018/8364848

Li X, Wang X, Guo Y, Deng N, Zheng P, Xu Q, et al. Regulation of endothelial nitric oxide synthase and asymmetric dimethylarginine by matrine attenuates isoproterenol-induced acute myocardial injury in rats. J Pharm Pharmacol. 2012;64(8):1107-18. https://doi.org/10.1111/j.2042-7158.2012.01502.x PMid:22775214 DOI: https://doi.org/10.1111/j.2042-7158.2012.01502.x

Zhou R, Ma P, Xiong A, Xu Y, Wang Y, Xu Q. Protective effects of low-dose rosuvastatin on isoproterenol-induced chronic heart failure in rats by regulation of DDAH-ADMA-NO pathway. Cardiovasc Ther. 2017;35(2):e12241. https://doi.org/10.1111/1755-5922.12241 PMid:27957828 DOI: https://doi.org/10.1111/1755-5922.12241

Marra M, Marchegiani F, Ceriello A, Sirolla C, Boemi M, Franceschi C, et al. Chronic renal impairment and DDAH2- 1151 A/C polymorphism determine ADMA levels in Type 2 diabetic subjects. Nephrol Dial Transplant. 2013;28(4):964-71. https://doi.org/10.1093/ndt/gfs516 PMid:23129820 DOI: https://doi.org/10.1093/ndt/gfs516

Dayem SM, Battah AA, Bohy AE, Ahmed S, Hamed M, Fattah SN. Nitric oxide gene polymorphism is a risk factor for diabetic nephropathy and atherosclerosis in Type 1 diabetic patients. Open Access Maced J Med Sci. 2019;7(19):3132-8. https://doi.org/10.3889/oamjms.2019.831 PMid:31949504 DOI: https://doi.org/10.3889/oamjms.2019.831

Elfi EF, Decroli E, Nasrul E, Yanwirasti Y, Darwin E. The risk factors of coronary heart disease and its relationship with endothelial nitric oxide synthase. Open Access Maced J Med Sci. 2021;9(B):451-6. https://doi.org/10.3889/oamjms.2021.6062 DOI: https://doi.org/10.3889/oamjms.2021.6062

Ohta T, Hasebe N, Tsuji S, Izawa K, Jin YT, Kido S, et al. Unequal effects of renin-angiotensin system inhibitors in acute cardiac dysfunction induced by isoproterenol. Am J Physiol Heart Circ Physiol. 2004;287(6):H2914-21. https://doi.org/10.1152/ajpheart.00221.2004 PMid:15297251 DOI: https://doi.org/10.1152/ajpheart.00221.2004

Delles C, Schneider MP, John S, Gekle M, Schmieder RE. Angiotensin converting enzyme inhibition and angiotensin II AT1-receptor blockade reduce the levels of asymmetrical N(G), N(G)-dimethylarginine in human essential hypertension. Am J Hypertens. 2002;15(7):590-3. https://doi.org/10.1016/s0895-7061(02)02278-1 PMid:12118904 DOI: https://doi.org/10.1016/S0895-7061(02)02278-1

Gamboa JL, Pretorius M, Sprinkel KC, Brown NJ, Ikizler TA. Angiotensin converting enzyme inhibition increases ADMA concentration in patients on maintenance hemodialysis-a randomized cross-over study. BMC Nephrol. 2015;16:167. https://doi.org/10.1186/s12882-015-0162-x PMid:26494370 DOI: https://doi.org/10.1186/s12882-015-0162-x

Ancion A, Tridetti J, Trung ML, Oury C, Lancellotti P. A review of the role of bradykinin and nitric oxide in the cardioprotective action of angiotensin-converting enzyme inhibitors: Focus on perindopril. Cardiol Ther. 2019;8(2):179-91. https://doi.org/10.1007/s40119-019-00150-w PMid:31578675 DOI: https://doi.org/10.1007/s40119-019-00150-w

Larsen BT, Bubolz AH, Mendoza SA, Pritchard KA Jr., Gutterman DD. Bradykinin-induced dilation of human coronary arterioles requires NADPH oxidase-derived reactive oxygen species. Arterioscler Thromb Vasc Biol. 2009;29(5):739-45. https://doi.org/10.1161/atvbaha.108.169367 PMid:19213944 DOI: https://doi.org/10.1161/ATVBAHA.108.169367

Luo Z, Teerlink T, Griendling K, Aslam S, Welch WJ, Wilcox CS. Angiotensin II and NADPH oxidase increase ADMA in vascular smooth muscle cells. Hypertension. 2010;56(3):498-504. https://doi.org/10.1161/hypertensionaha.110.152959 PMid:20696982 DOI: https://doi.org/10.1161/HYPERTENSIONAHA.110.152959

Wilcox CS. Asymmetric dimethylarginine and reactive oxygen species: Unwelcome twin visitors to the cardiovascular and kidney disease tables. Hypertension. 2012;59(2):375-81. https://doi.org/10.1161/hypertensionaha.111.187310 PMid:22215715 DOI: https://doi.org/10.1161/HYPERTENSIONAHA.111.187310

Firinu D, Bassareo PP, Zedda AM, Barca MP, Crisafulli A, Mercuro G, Del Giacco S. Impaired endothelial function in hereditary angioedema during the symptom-free period. Front Physiol. 2018;9:523. https://doi.org/10.3389/fphys.2018.00523 PMid:29867566 DOI: https://doi.org/10.3389/fphys.2018.00523




How to Cite

Aliska G, Dhuha A, Rahmatini R, Hamdani R, Afriani N, Tofrizal T, Ali H, Pratiwi N, Nuranisyah V, Mahata LE, Kurnia D. Ramipril Increases Adma Concentration in Acute Myocardial Infarction in Rats Induced by Isoproterenol. Open Access Maced J Med Sci [Internet]. 2021 Aug. 21 [cited 2024 Mar. 5];9(A):693-7. Available from: https://oamjms.eu/index.php/mjms/article/view/6572

Most read articles by the same author(s)

1 2 > >>