Effect of the amino acids L-arginine and N-acetyl-L-cysteine on the functional characteristics of cardiovascular system parameters in rats with experimental type 1 diabetes mellitus
DOI:
https://doi.org/10.14739/mmt.2026.1.337021Keywords:
cardiomyopathy, myocardial remodeling, left ventricle, L-arginine, N-acetyl-L-cysteine, diabetes mellitus type 1, echocardiography, blood pressure, ratsAbstract
The aim was to investigate the effects of L-arginine and N-acetyl-L-cysteine on the structural and functional characteristics of cardiovascular system parameters in rats with experimental type 1 diabetes mellitus (DM1).
Methods and techniques. DM1 was induced in old male Wistar rats by a single 45 mg/kg streptozotocin. After 6 weeks, animals with DM1 were divided into 3 subgroups: without amino acid administration, rats with L-arginine and rats with N-acetyl-L-cysteine. To achieve the aim, blood pressure measurements and echocardiography were performed.
Results. In rats with DM1, a significant increase in systolic (by 24 %) and diastolic (by 17 %) blood pressure was observed at the 6th week of the experiment. Left ventricular dilatation was also found, accompanied by an increase in end-diastolic (by 20 %) and end-systolic (by 61 %) volumes, as well as a decrease in ejection fraction (by 6 %). At week 8, in rats without correction, blood pressure continued to increase (systolic by 7 %, diastolic by 9 %), and systolic dysfunction also progressed. Administration of L-arginine for 2 weeks normalized blood pressure (decrease by 12–16 %) and reduced left ventricular dilatation. L-arginine also improved systolic function (increase in ejection fraction by 6 %). N-acetyl-L-cysteine also reduced pressure but had no significant effect on echocardiographic parameters.
Conclusions. Against the background of the development of experimental type 1 diabetes mellitus in rats, cardiomyopathy with dilatation of the left ventricle and a decrease in its systolic function is formed by the 6th week. These changes occur in parallel with a significant increase in blood pressure and a decrease in heart rate. In rats with experimental diabetes mellitus, after 8 weeks, signs of left ventricular dilatation remained without statistically significant changes compared to the indicators of the 6th week, however, progression of systolic dysfunction was observed against the background of a further increase in blood pressure. Administration of L-arginine to rats with diabetes mellitus for 2 weeks statistically significantly reduced blood pressure and decreased manifestations of left ventricular dilatation comparable to rats with diabetes mellitus of 8 weeks duration without correction. Administration of N-acetyl-L-cysteine reduced blood pressure in the corresponding subgroup, however, no statistically significant effect on echocardiographic parameters was found compared to the 8-week group without correction.
References
Wang M, Li Y, Li S, Lv J. Endothelial Dysfunction and Diabetic Cardiomyopathy. Front Endocrinol (Lausanne). 2022;13:851941. doi: https://doi.org/10.3389/fendo.2022.851941
Syed FZ. Type 1 diabetes mellitus. Ann Intern Med. 2022;175(3):ITC33-48. doi: https://doi.org/10.7326/AITC202203150
Heather LC, Gopal K, Srnic N, Ussher JR. Redefining Diabetic Cardiomyopathy: Perturbations in Substrate Metabolism at the Heart of Its Pathology. Diabetes. 2024;73(5):659-70. doi: https://doi.org/10.2337/dbi23-0019
Gawrys J, Gajecki D, Szahidewicz-Krupska E, Doroszko A. Intraplatelet L-Arginine-Nitric Oxide Metabolic Pathway: From Discovery to Clinical Implications in Prevention and Treatment of Cardiovascular Disorders. Oxid Med Cell Longev. 2020;2020:1015908. doi: https://doi.org/10.1155/2020/1015908
Sloun BV, Goossens GH, Erdos B, Lenz M, Riel NV, Arts IC. The Impact of Amino Acids on Postprandial Glucose and Insulin Kinetics in Humans: A Quantitative Overview. Nutrients. 2020;12(10):3211. doi: https://doi.org/10.3390/nu12103211
Loscalzo J. Nitric oxide in vascular biology: elegance in complexity. J Clin Invest. 2024;134(4):e176747. doi: https://doi.org/10.1172/JCI176747
Bhattacharya R, Saini S, Ghosh S, Roy P, Ali N, Parvez MK, et al. Organosulfurs, S-allyl cysteine and N-acetyl cysteine sequester di-carbonyls and reduces carbonyl stress in HT22 cells. Sci Rep. 2023;13(1):13071. doi: https://doi.org/10.1038/s41598-023-40291-6
European Union. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Official Journal of the European Union, L276/33, 2010.
Verkhovna Rada of Ukraine. [On the Protection of Animals from Brutal Treatment]. Law of Ukraine dated 2006 Feb 21, No. 3447-IV. Available from: https://zakon.rada.gov.ua/laws/show/3447-15?lang=en#Text
Furman BL. Streptozotocin-Induced Diabetic Models in Mice and Rats. Curr Protoc. 2021;1(4):e78. doi: https://doi.org/10.1002/cpz1.78
Kolesnyk YM, Kolesnyk MY, Hancheva OV, Isachenko MI. Left ventricular remodeling in normotensive Wistar rats exposed to intermittent hypoxia of different duration. Pathologia. 2023;20(1):5-13. doi: https://doi.org/10.14739/2310-1237.2023.1.277406
De Blasio MJ, Huynh N, Deo M, Dubrana LE, Walsh J, Willis A, et al. Defining the Progression of Diabetic Cardiomyopathy in a Mouse Model of Type 1 Diabetes. Front Physiol. 2020;11:124. doi: https://doi.org/10.3389/fphys.2020.00124
Zou X, Zhang L, Wang L, Wang S, Zeng Y. Exploring the Causality of Type 1 Diabetes and Stroke Risk: A Mendelian Randomization Study and Meta-analysis. Mol Neurobiol. 2023;60(12):6814-25. doi: https://doi.org/10.1007/s12035-023-03517-2
Zaveri MP, Perry JC, Schuetz TM, Memon MD, Faiz S, Cancarevic I. Diabetic Cardiomyopathy as a Clinical Entity: Is It a Myth? Cureus. 2020;12(10):e11100. doi: https://doi.org/10.7759/cureus.11100
Galis P, Bartosova L, Farkasova V, Bartekova M, Ferenczyova K, Rajtik T. Update on clinical and experimental management of diabetic cardiomyopathy: addressing current and future therapy. Front Endocrinol (Lausanne). 2024;15:1451100. doi: https://doi.org/10.3389/fendo.2024.1451100
Zhao X, Liu S, Wang X, Chen Y, Pang P, Yang Q, et al. Diabetic cardiomyopathy: Clinical phenotype and practice. Front Endocrinol (Lausanne). 2022;13:1032268. doi: https://doi.org/10.3389/fendo.2022.1032268
Malone MA, Schocken DD, Hanna SK, Liang X, Malone JI. Diabetes-induced bradycardia is an intrinsic metabolic defect reversed by carnitine. Metabolism. 2007;56(8):1118-23. doi: https://doi.org/10.1016/j.metabol.2007.04.005
Gao S, Liu XP, Li TT, Chen L, Feng YP, Wang YK, et al. Animal models of heart failure with preserved ejection fraction (HFpEF): from metabolic pathobiology to drug discovery. Acta Pharmacol Sin. 2024;45(1):23-35. doi: https://doi.org/10.1038/s41401-023-01152-0
Serhiyenko V, Serhiyenko A. [Diabetes mellitus and congestive heart failure]. International journal of endocrinology (Ukraine). 2022;18(1):57-69. Ukrainian. doi: https://doi.org/10.22141/2224-0721.18.1.2022.1146
Zhao Z, Hou C, Ye X, Cheng J. Echocardiographic Changes in Newly Diagnosed Type 2 Diabetes Mellitus Patients with and without Hypertension. Med Sci Monit. 2020;26:e918972. doi: https://doi.org/10.12659/MSM.918972
Forzano I, Avvisato R, Varzideh F, Jankauskas SS, Cioppa A, Mone P, et al. L-Arginine in diabetes: clinical and preclinical evidence. Cardiovasc Diabetol. 2023 Apr 18;22(1):89. doi: https://doi.org/10.1186/s12933-023-01827-2. Erratum in: Cardiovasc Diabetol. 2023;22(1):117. doi: https://doi.org/10.1186/s12933-023-01852-1
Belenichev I, Popazova O, Bukhtiyarova N, Savchenko D, Oksenych V, Kamyshnyi O. Modulating Nitric Oxide: Implications for Cytotoxicity and Cytoprotection. Antioxidants (Basel). 2024;13(5):504. doi: https://doi.org/10.3390/antiox13050504
Pan KL, Hsu YC, Chang ST, Chung CM, Lin CL. The Role of Cardiac Fibrosis in Diabetic Cardiomyopathy: From Pathophysiology to Clinical Diagnostic Tools. Int J Mol Sci. 2023;24(10):8604. doi: https://doi.org/10.3390/ijms24108604
Shou Y, Li X, Fang Q, Xie A, Zhang Y, Fu X, et al. Progress in the treatment of diabetic cardiomyopathy, a systematic review. Pharmacol Res Perspect. 2024;12(2):e1177. doi: https://doi.org/10.1002/prp2.1177
Downloads
Additional Files
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Ye. V. Kadzharian, M. Yu. Kolesnyk, M. I. Isachenko, Yu. M. Kolesnyk

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The work is provided under the terms of the Public Offer and of Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). This license allows an unlimited number of persons to reproduce and share the Licensed Material in all media and formats. Any use of the Licensed Material shall contain an identification of its Creator(s) and must be for non-commercial purposes only.











