{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:08:09Z","timestamp":1791655689861,"version":"4.3.4"},"reference-count":66,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland","award":["Theme 18, 2023, 2024"],"award-info":[{"award-number":["Theme 18, 2023, 2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We showed recently that the adenosine system and nitric oxide (NO) can interact differently in the control of renal function in normoglycaemia (NG) versus streptozotocin-induced diabetes (DM). Herein, we investigated if this relationship is modulated by dietary betaine (Bet, food compound possessing antioxidant and anti-inflammatory properties), to examine if adenosine receptor signalling in NG and DM females is altered by chronic Bet supplementation. The effects of intravenous infusion of theophylline, non-selective adenosine receptor antagonist, were examined in anaesthetised Sprague\u2013Dawley female rats, pretreated for 2 weeks with Bet alone or combined with 4-day NO synthesis blockade with L-NAME (Bet + L-NAME). Renal blood flow (RBF, ultrasound artery probe), perfusion of the cortex, outer (OM-BF) and inner medulla (IM-BF; laser-Doppler technique), and tissue NO signal (selective electrode) were determined along with renal excretion. Bet and Bet + L-NAME decreased baseline RBF irrespective of glycaemia, whereas Bet lowered (NG) or elevated (DM) basal OM-BF; Bet + L-NAME treatment abolished these effects. Baseline sodium excretion decreased after Bet and Bet + L-NAME in NG only. Bet modified theophylline effects: IM-BF was lowered in DM rats, while tissue NO changes shown in the control were modified: NO increased in NG and decreased in DM. In NG, these effects were abolished by Bet + L-NAME. Bet pretreatment did not alter diuresis, natriuresis and kaliuresis, but after Bet + L-NAME these parameters increased (NG) or decreased (DM). Dietary Bet has the potential to affect renal medullary blood circulation; however, the eventual effect depends on glycaemia. Bet can modify renal functional changes induced by the interplay of the adenosine and NO systems, both in rats with normoglycaemia and streptozotocin diabetes.<\/jats:p>","DOI":"10.3390\/ijms27094076","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T01:12:09Z","timestamp":1777857129000},"page":"4076","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Betaine Alters the Interplay of the Adenosine and NO Systems in the Control of Renal Regional Haemodynamics and Excretion in Diabetic Female Rats"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7545-7150","authenticated-orcid":false,"given":"Leszek","family":"Dobrowolski","sequence":"first","affiliation":[{"name":"Department of Renal and Body Fluid Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 A. Pawi\u0144skiego Street, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Volodymyrivna","family":"Monchakivska","sequence":"additional","affiliation":[{"name":"Department of Renal and Body Fluid Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 A. Pawi\u0144skiego Street, 02-106 Warsaw, Poland"},{"name":"Departments of Biochemistry, Educational and Scientific Centre, Institute of Biology and Medicine, Taras Shevchenko National University of Kyiv, 02000 Kyiv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6732-2560","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Rogozi\u0144ska","sequence":"additional","affiliation":[{"name":"MASDIAG Ltd., 33 S. \u017beromskiego Street, 01-882 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Kowalski","sequence":"additional","affiliation":[{"name":"MASDIAG Ltd., 33 S. \u017beromskiego Street, 01-882 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Kuczeriszka","sequence":"additional","affiliation":[{"name":"Department of Renal and Body Fluid Physiology, Mossakowski Medical Research Institute, Polish Academy of Sciences, 5 A. 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Pharmacol. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.bcp.2017.06.130","article-title":"Sulodexide prevents activation of the PLA2\/COX-2\/VEGF inflammatory pathway in human retinal endothelial cells by blocking the effect of AGE\/RAGE","volume":"142","author":"Giurdanella","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"19","DOI":"10.5114\/oku\/177689","article-title":"Vasoprotective Effect of Sulodexide in Diabetic Retinopathy","volume":"2023","author":"Dobrowolski","year":"2023","journal-title":"Ophthalmology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1002\/cbin.12239","article-title":"Oxidative stress disrupts vascular microenvironmental homeostasis affecting the development of atherosclerosis","volume":"48","author":"Shao","year":"2024","journal-title":"Cell Biol. Int."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e651","DOI":"10.1002\/mco2.651","article-title":"Endothelial dysfunction: Molecular mechanisms and clinical implications","volume":"5","author":"Wang","year":"2024","journal-title":"Medcomm"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"30392","DOI":"10.1074\/jbc.M103702200","article-title":"Insulin-stimulated activation of eNOS is independent of Ca2+ but requires phosphorylation by Akt at Ser1179","volume":"276","author":"Montagnani","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ahmad, A., Dempsey, S.K., Daneva, Z., Azam, M., Li, N., Li, P.-L., and Ritter, J.K. (2018). Role of Nitric Oxide in the Cardiovascular and Renal Systems. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092605"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.ccc.2019.12.009","article-title":"Nitric Oxide and Endothelial Dysfunction","volume":"36","author":"Cyr","year":"2020","journal-title":"Crit. Care Clin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0895-7061(97)00360-9","article-title":"Gender Differences in the Renal Nitric Oxide (NO) System Dissociation Between Expression of Endothelial NO Synthase and Renal Hemodynamic Response to NO Synthase Inhibition","volume":"11","author":"Reckelhoff","year":"1998","journal-title":"Am. J. Hypertens."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gonzalez-Vicente, A., and Garvin, J.L. (2017). Effects of Reactive Oxygen Species on Tubular Transport along the Nephron. Antioxidants, 6.","DOI":"10.3390\/antiox6020023"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6871081","DOI":"10.1155\/2017\/6871081","article-title":"Effects of Nitric Oxide on Renal Proximal Tubular Na+ Transport","volume":"2017","author":"Satoh","year":"2017","journal-title":"BioMed Res. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"R61","DOI":"10.1152\/ajpregu.00526.2009","article-title":"Renal NOS activity, expression, and localization in male and female spontaneously hypertensive rats","volume":"298","author":"Sullivan","year":"2010","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"F179","DOI":"10.1152\/ajprenal.00455.2014","article-title":"Reactive oxygen species as important determinants of medullary flow, sodium excretion, and hypertension","volume":"308","author":"Cowley","year":"2015","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1161\/HYPERTENSIONAHA.109.128827","article-title":"Effects of Renal Perfusion Pressure on Renal Medullary Hydrogen Peroxide and Nitric Oxide Production","volume":"53","author":"Jin","year":"2009","journal-title":"Hypertension"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5549","DOI":"10.1002\/ptr.8335","article-title":"Limitations and Challenges of Antioxidant Therapy","volume":"38","author":"Masoud","year":"2024","journal-title":"Phytother. Res."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Liu, J., Qin, L., Zheng, J., Tong, L., Lu, W., Lu, C., Sun, J., Fan, B., and Wang, F. (2023). Research Progress on the Relationship between Vitamins and Diabetes: Systematic Review. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242216371"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"947","DOI":"10.7150\/ijbs.37861","article-title":"Vitamin A deficiency causes islet dysfunction by inducing islet stellate cell activation via cellular retinol binding protein 1","volume":"16","author":"Zhou","year":"2020","journal-title":"Int. J. Biol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1074\/jbc.M114.616763","article-title":"Vitamin A Deficiency Causes Hyperglycemia and Loss of Pancreatic \u03b2-Cell Mass","volume":"290","author":"Trasino","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Saeed, A., Dullaart, R.P.F., Schreuder, T.C.M.A., Blokzijl, H., and Faber, K.N. (2017). Disturbed Vitamin A Metabolism in Non-Alcoholic Fatty Liver Disease (NAFLD). Nutrients, 10.","DOI":"10.3390\/nu10010029"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.2337\/dc09-2321","article-title":"Association of Vitamin D With Insulin Resistance and \u03b2-Cell Dysfunction in Subjects at Risk for Type 2 Diabetes","volume":"33","author":"Kayaniyil","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"S589","DOI":"10.1016\/j.dsx.2017.04.009","article-title":"Vitamin supplements in type 2 diabetes mellitus management: A review","volume":"11","author":"Yan","year":"2017","journal-title":"Diabetes Metab. Syndr. Clin. Res. Rev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1111\/j.1463-1326.2007.00710.x","article-title":"Role of vitamin D in the pathogenesis of type 2 diabetes mellitus","volume":"10","author":"Palomer","year":"2007","journal-title":"Diabetes Obes. Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1161\/01.CIR.0000055186.40785.C4","article-title":"Vitamin E Reduces Progression of Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice With Established Vascular Lesions","volume":"107","author":"Cyrus","year":"2003","journal-title":"Circulation"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Arumugam, M.K., Paal, M.C., Donohue, T.M., Ganesan, M., Osna, N.A., and Kharbanda, K.K. (2021). Beneficial Effects of Betaine: A Comprehensive Review. Biology, 10.","DOI":"10.3390\/biology10060456"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3481","DOI":"10.3390\/nu5093481","article-title":"The Metabolic Burden of Methyl Donor Deficiency with Focus on the Betaine Homocysteine Methyltransferase Pathway","volume":"5","author":"Obeid","year":"2013","journal-title":"Nutrients"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e00579","DOI":"10.1002\/mgg3.579","article-title":"The protective impact of betaine on the tissue structure and renal function in isoproterenol-induced myocardial infarction in rat","volume":"7","author":"Ghartavol","year":"2019","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"112946","DOI":"10.1016\/j.biopha.2022.112946","article-title":"The anti-diabetic potential of betaine. Mechanisms of action in rodent models of type 2 diabetes","volume":"150","author":"Szkudelska","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Pelpolage, S.W., Sasaki, R., Shimada, K., Nagura, T., Uchino, H., Han, K.-H., and Fukushima, M. (2024). Oral Supplementation with Betaine Powder Ameliorated High Blood Pressure in Spontaneously Hypertensive Rats. Metabolites, 14.","DOI":"10.3390\/metabo14070390"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1097\/HJH.0000000000004085","article-title":"Betaine protects cerebral microvascular endothelium and ameliorates hypertension-induced cognitive dysfunction via upregulation of the endothelial nitric oxide synthase\/nitric monoxide signaling pathway","volume":"43","author":"Sun","year":"2025","journal-title":"J. Hypertens."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/j.bbagen.2016.02.001","article-title":"Betaine chemistry, roles, and potential use in liver disease","volume":"1860","author":"Day","year":"2016","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Gen. Subj."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"F590","DOI":"10.1152\/ajprenal.00051.2003","article-title":"Vasoconstrictor and vasodilator effects of adenosine in the kidney","volume":"285","author":"Hansen","year":"2003","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1111\/j.1523-1755.2004.00490.x","article-title":"Gene expression of adenosine receptors along the nephron","volume":"65","author":"Vitzthum","year":"2004","journal-title":"Kidney Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s11302-013-9359-2","article-title":"Purinergic signalling and diabetes","volume":"9","author":"Burnstock","year":"2013","journal-title":"Purinergic Signal."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/nrendo.2015.10","article-title":"Adenosine signalling in diabetes mellitus\u2014pathophysiology and therapeutic considerations","volume":"11","author":"Antonioli","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1007\/s11154-021-09668-8","article-title":"Therapeutic potentials of agonist and antagonist of adenosine receptors in type 2 diabetes","volume":"22","author":"Sanni","year":"2021","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"F108","DOI":"10.1152\/ajprenal.00108.2008","article-title":"Acute inhibition of the betaine transporter by ATP and adenosine in renal MDCK cells","volume":"295","author":"Kempson","year":"2008","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s11302-013-9400-5","article-title":"Purinergic signalling in the kidney in health and disease","volume":"10","author":"Burnstock","year":"2013","journal-title":"Purinergic Signal."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kuczeriszka, M., and Dobrowolski, L. (2024). Sex Dependence in Control of Renal Haemodynamics and Excretion in Streptozotocin Diabetic Rats\u2014Role of Adenosine System and Nitric Oxide. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25147699"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1161\/HYPERTENSIONAHA.124.21711","article-title":"Renal Medulla in Hypertension","volume":"81","author":"Cowley","year":"2024","journal-title":"Hypertension"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1111\/cts.12402","article-title":"Chronic Kidney Disease Alters Vitamin A Homeostasis via Effects on Hepatic RBP4 Protein Expression and Metabolic Enzymes","volume":"9","author":"Jing","year":"2016","journal-title":"Clin. Transl. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9923689","DOI":"10.1155\/ghe3\/9923689","article-title":"Serum Vitamin E Status in Patients With Type 2 Diabetes Mellitus Among Bangladeshi Population","volume":"2025","author":"Ripon","year":"2025","journal-title":"Glob. Heal. Epidemiol. Genom."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1136\/bmj.311.7013.1124","article-title":"Increased risk of non-insulin dependent diabetes mellitus at low plasma vitamin E concentrations: A four year follow up study in men","volume":"311","author":"Salonen","year":"1995","journal-title":"BMJ"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.biopha.2005.05.002","article-title":"Effect of \u03b1-tocopherol on the metabolic control and oxidative stress in female type 2 diabetics","volume":"59","year":"2005","journal-title":"Biomed. Pharmacother."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Wronka, M., Krzemi\u0144ska, J., M\u0142ynarska, E., Rysz, J., and Franczyk, B. (2022). The Influence of Lifestyle and Treatment on Oxidative Stress and Inflammation in Diabetes. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232415743"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1161\/01.HYP.28.2.297","article-title":"Neural Nitric Oxide Synthase in the Renal Medulla and Blood Pressure Regulation","volume":"28","author":"Mattson","year":"1996","journal-title":"Hypertension"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1097\/00041552-199807000-00016","article-title":"Role of macula densa NOS in tubuloglomerular feedback","volume":"7","author":"Wilcox","year":"1998","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_49","first-page":"149","article-title":"Renal tissue NO and intrarenal haemodynamics during experimental variations of NO content in anaesthetised rats","volume":"58","author":"Sadowski","year":"2007","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1748-1716.2010.02222.x","article-title":"Interaction of nitric oxide and the cytochrome P-450 system on blood pressure and renal function in the rat: Dependence on sodium intake","volume":"201","author":"Kuczeriszka","year":"2010","journal-title":"Acta Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"R1573","DOI":"10.1152\/ajpregu.00429.2007","article-title":"Sex and sex hormones influence the development of albuminuria and renal macrophage infiltration in spontaneously hypertensive rats","volume":"293","author":"Sullivan","year":"2007","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.niox.2020.08.003","article-title":"Interplay of the adenosine system and NO in control of renal haemodynamics and excretion: Comparison of normoglycaemic and streptozotocin diabetic rats","volume":"104\u2013105","author":"Kuczeriszka","year":"2020","journal-title":"Nitric Oxide"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"R13","DOI":"10.1152\/ajpregu.00321.2002","article-title":"Importance of the renal medullary circulation in the control of sodium excretion and blood pressure","volume":"284","author":"Mattson","year":"2003","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"F1121","DOI":"10.1152\/ajprenal.00265.2002","article-title":"Paradoxes of nitric oxide in the diabetic kidney","volume":"284","author":"Komers","year":"2003","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1159\/000329054","article-title":"Endothelin, nitric oxide, and reactive oxygen species in diabetic kidney disease","volume":"172","author":"Pollock","year":"2011","journal-title":"Contrib. Nephrol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/978-3-540-89615-9_6","article-title":"Adenosine receptors and the heart: Role in regulation of coronary blood flow and cardiac electrophysiology","volume":"193","author":"Mustafa","year":"2009","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s00395-021-00859-7","article-title":"Adenosine and adenosine receptor-mediated action in coronary microcirculation","volume":"116","author":"Zhang","year":"2021","journal-title":"Basic Res. Cardiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1007\/s11033-024-09246-6","article-title":"Therapeutic potency of A1 adenosine receptor antagonists in the treatment of cardiovascular diseases, current status and perspectives","volume":"51","author":"Bahreyni","year":"2024","journal-title":"Mol. Biol. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12933-016-0349-x","article-title":"Upregulation of inducible NO synthase by exogenous adenosine in vascular smooth muscle cells activated by inflammatory stimuli in experimental diabetes","volume":"15","author":"Nassi","year":"2016","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1111\/1440-1681.13303","article-title":"Altered renal medullary blood flow: A key factor or a parallel event in control of sodium excretion and blood pressure?","volume":"47","author":"Sadowski","year":"2020","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"F651","DOI":"10.1152\/ajprenal.1993.265.5.F651","article-title":"Interactions of adenosine A1 receptor-mediated renal vasoconstriction with endogenous nitric oxide and ANG II","volume":"265","author":"Barrett","year":"1993","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"F340","DOI":"10.1152\/ajprenal.1999.276.3.F340","article-title":"Adenosine-induced renal vasoconstriction in diabetes mellitus rats: Role of nitric oxide","volume":"276","author":"Pflueger","year":"1999","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Sousa, J.B., and Diniz, C. (2017). The Adenosinergic System as a Therapeutic Target in the Vasculature: New Ligands and Challenges. Molecules, 22.","DOI":"10.3390\/molecules22050752"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"113686","DOI":"10.1016\/j.bcp.2019.113686","article-title":"S-Nitrosothiols as potential therapeutics to induce a mobilizable vascular store of nitric oxide to counteract endothelial dysfunction","volume":"173","author":"Zhou","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s11892-005-0054-8","article-title":"Pathogenic role of nitric oxide alterations in diabetic nephropathy","volume":"5","author":"Prabhakar","year":"2005","journal-title":"Curr. Diabetes Rep."},{"key":"ref_66","first-page":"160","article-title":"Amperometric detection of nitric oxide","volume":"1","author":"Zhang","year":"2000","journal-title":"Mod. AspImmunobiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/4076\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T17:27:49Z","timestamp":1778520469000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/9\/4076"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,2]]},"references-count":66,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27094076"],"URL":"https:\/\/doi.org\/10.3390\/ijms27094076","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,2]]}}}