Login Register Cart 0
Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Blockade of Renin Angiotensin System Ameliorates the Cardiac Arrhythmias and Sympathetic Neural Remodeling in Hearts of Type 2 DM Rat Model

Author(s): Yomna M. Yehya, Abdelaziz M. Hussein*, Khaled Ezam, Elsayed A. Eid, Eman M. Ibrahim, Mohamed A.F.E. Sarhan, Aya Elsayed and Mohamed E. Sarhan

Volume 20, Issue 3, 2020

Page: [464 - 478] Pages: 15

DOI: 10.2174/1871530319666190809150921

Price: $65

Abstract

Objective: The present study was designed to investigate the effects of renin angiotensin system (RAS) blockade on cardiac arrhythmias and sympathetic nerve remodelling in heart tissues of type 2 diabetic rats.

Methods: Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group: normal rats, b) DM group; after type 2 diabetes induction, rats received 2ml oral saline daily for 4 weeks, c) DM+ ACEi: after type 2 diabetes induction, rats were treated with enalapril (10 mg/kg, orally for 4 weeks) and d) DM+ ARBs: after type 2 diabetes induction, rats were treated with losartan (30 mg/kg, orally for 4 weeks).

Results: In type 2 diabetic rats, the results demonstrated significant prolongation in Q-T interval and elevation of blood sugar, HOMA-IR index, TC, TGs, LDL, serum CK-MB, myocardial damage, myocardial MDA, myocardial norepinephrine and tyrosine hydroxylase (TH) density with significant reduction in serum HDL, serum insulin and myocardial GSH and CAT. On the other hand, blockade of RAS at the level of either ACE by enalapril or angiotensin (Ag) receptors by losartan resulted in significant improvement in ECG parameters (Q-T), cardiac enzymes (CK-MB), cardiac morphology, myocardial oxidative stress (low MDA, high CAT and GSH) and myocardial TH density.

Conclusion: RAS plays a role in the cardiac sympathetic nerve sprouting and cardiac arrhythmias induced by type 2 DM and its blockade might have a cardioprotective effect via attenuation of sympathetic nerve fibres remodelling, myocardial norepinephrine contents and oxidative stress.

Keywords: Type 2 DM, oxidative stress, diabetic cardiomyopathy, norepinephrine, renin angiotensin system, sympathetic remodelling.

« Previous Next »
Graphical Abstract

[1]
WHO Key facts on diabetes; 2018, World Health Organization. https://www.who.int/news-room/fact-sheets/detail/diabetes
[2]
Vinik, A.I.; Erbas, T.; Casellini, C.M. Diabetic cardiac autonomic neuropathy, inflammation and cardiovascular disease. J. Diabetes Investig., 2013, 4(1), 4-18.
[http://dx.doi.org/10.1111/jdi.12042] [PMID: 23550085]
[3]
Vinik, A.I.; Ziegler, D. Diabetic cardiovascular autonomic neuropathy. Circulation, 2007, 115(3), 387-397.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.634949] [PMID: 17242296]
[4]
Dhalla, N.S.; Adameova, A.; Kaur, M. Role of catecholamine oxidation in sudden cardiac death. Fundam. Clin. Pharmacol., 2010, 24(5), 539-546.
[http://dx.doi.org/10.1111/j.1472-8206.2010.00836.x] [PMID: 20584205]
[5]
Goyal, B.R.; Mesariya, P.; Goyal, R.K.; Mehta, A.A. Effect of telmisartan on cardiovascular complications associated with streptozotocin diabetic rats. Mol. Cell. Biochem., 2008, 314(1-2), 123-131.
[http://dx.doi.org/10.1007/s11010-008-9772-y] [PMID: 18425420]
[6]
Adameova, A.; Elimban, V.; Rodriguez-Leyva, D.; Tappia, P.S.; Dhalla, N.S. Susceptibility of diabetic heart to catecholamine-induced arrhythmias is independent of contractile dysfunction. Serb. J. Exp. Clin. Res., 2014, 15(2), 71-78.
[http://dx.doi.org/10.2478/sjecr-2014-0009]
[7]
Schmieder, R.E.; Hilgers, K.F.; Schlaich, M.P.; Schmidt, B.M. Renin-angiotensin system and cardiovascular risk. Lancet, 2007, 369(9568), 1208-1219.
[http://dx.doi.org/10.1016/S0140-6736(07)60242-6] [PMID: 17416265]
[8]
Leri, A.; Fiordaliso, F.; Setoguchi, M.; Limana, F.; Bishopric, N.H.; Kajstura, J.; Webster, K.; Anversa, P. Inhibition of p53 function prevents renin-angiotensin system activation and stretch-mediated myocyte apoptosis. Am. J. Pathol., 2000, 157(3), 843-857.
[http://dx.doi.org/10.1016/S0002-9440(10)64598-1] [PMID: 10980124]
[9]
Crabos, M.; Roth, M.; Hahn, A.W.; Erne, P. Characterization of angiotensin II receptors in cultured adult rat cardiac fibroblasts. Coupling to signaling systems and gene expression. J. Clin. Invest., 1994, 93(6), 2372-2378.
[http://dx.doi.org/10.1172/JCI117243] [PMID: 8200970]
[10]
Hussein, Ael-A.; Omar, N.M.; Sakr, H.; Elsamanoudy, A.Z.; Shaheen, D. Modulation of metabolic and cardiac dysfunctions by insulin sensitizers and angiotensin receptor blocker in rat model of type 2 diabetes mellitus. Can. J. Physiol. Pharmacol., 2011, 89(3), 216-226.
[http://dx.doi.org/10.1139/Y11-012] [PMID: 21423295]
[11]
El-Mousalamy, A.M.D.; Hussein, A.A.M.; Mahmoud, S.A.; Abdelaziz, A.; Shaker, G. (2016) Aqueous and Methanolic Extracts of Palm Date Seeds and Fruits (Phoenix dactylifera) Protects against Diabetic Nephropathy in Type II Diabetic Rats. Biochem. Physiol., 5, 205. 10.4172/2168-9652.1000205
[http://dx.doi.org/10.3892/etm.2013.1134] [PMID: 24137228]
[12]
Yang, Y.; Zhang, P.; Song, L.; Ruan, Y.; Xu, X.; Li, Y.; Zhou, Y.; Tian, Y.; Xu, Y.; Chen, Z. Comparison of three doses of enalapril in preventing left ventricular remodeling after acute myocardial infarction in the rat. Chin. Med. J. (Engl.), 2002, 115(3), 347-351.
[PMID: 11940361]
[13]
Kaneko, K.; Susic, D.; Nunez, E.; Frohlich, E.D. Losartan reduces cardiac mass and improves coronary flow reserve in the spontaneously hypertensive rat. J. Hypertens., 1996, 14(5), 645-653.
[http://dx.doi.org/10.1097/00004872-199605000-00015] [PMID: 8762209]
[14]
El-Wakf, A.; El-Habibi, E.; Barakat, N.; Attia, A.; Hussein, A. Cardiovascular Toxic Effects of Chlorpyrifos: A Possible Protective Role for Pomegranate Extracts. J Clin Toxicol, 2018, 8(374), 2161-0495.1000374..
[15]
Parasuraman, S.; Raveendran, R.; Kesavan, R. Blood sample collection in small laboratory animals. J. Pharmacol. Pharmacother., 2010, 1(2), 87-93.
[http://dx.doi.org/10.4103/0976-500X.72350] [PMID: 21350616]
[16]
Salgado, A.L.F.A.; Carvalho, Ld.; Oliveira, A.C.; Santos, V.N.; Vieira, J.G.; Parise, E.R. Insulin resistance index (HOMA-IR) in the differentiation of patients with non-alcoholic fatty liver disease and healthy individuals. Arq. Gastroenterol., 2010, 47(2), 165-169.
[http://dx.doi.org/10.1590/S0004-28032010000200009] [PMID: 20721461]
[17]
Yu, H.; Zhen, J.; Yang, Y.; Gu, J.; Wu, S.; Liu, Q. Ginsenoside Rg1 ameliorates diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress-induced apoptosis in a streptozotocin-induced diabetes rat model. J. Cell. Mol. Med., 2016, 20(4), 623-631.
[http://dx.doi.org/10.1111/jcmm.12739] [PMID: 26869403]
[18]
Taheri Rouhi, S.Z.; Sarker, M.M.R.; Rahmat, A.; Alkahtani, S.A.; Othman, F. The effect of pomegranate fresh juice versus pomegranate seed powder on metabolic indices, lipid profile, inflammatory biomarkers, and the histopathology of pancreatic islets of Langerhans in streptozotocin-nicotinamide induced type 2 diabetic Sprague-Dawley rats. BMC Complement. Altern. Med., 2017, 17(1), 156.
[http://dx.doi.org/10.1186/s12906-017-1667-6] [PMID: 28288617]
[19]
Naidu, P.B.; Ponmurugan, P.; Begum, M.S.; Mohan, K.; Meriga, B. RavindarNaik, R.; Saravanan, G. Diosgenin reorganises hyperglycaemia and distorted tissue lipid profile in high-fat diet-streptozotocin-induced diabetic rats. J. Sci. Food Agric., 2015, 95(15), 3177-3182.
[http://dx.doi.org/10.1002/jsfa.7057] [PMID: 25530163]
[20]
Grisanti, L.A. Diabetes and Arrhythmias: Pathophysiology, Mechanisms and Therapeutic Outcomes. Front. Physiol., 2018, 9, 1669.
[http://dx.doi.org/10.3389/fphys.2018.01669] [PMID: 30534081]
[21]
Malek, V.; Gaikwad, A.B. Telmisartan and thiorphan combination treatment attenuates fibrosis and apoptosis in preventing diabetic cardiomyopathy. Cardiovasc. Res., 2019, 115(2), 373-384.
[http://dx.doi.org/10.1093/cvr/cvy226] [PMID: 30184174]
[22]
Tiwari, S.; Ndisang, J.F. Upregulating Heme Oxygenase Improves Electrocardiographic and Hemodynamic Parameters by Potentiating Insulin Signaling in an Obese Model of Diabetic Cardiomyopathy. Can. J. Diabetes, 2015, 39(6), 538.
[http://dx.doi.org/10.1016/j.jcjd.2015.09.049]
[23]
Attia, H.M.; Taha, M. Protective effect of captopril on cardiac fibrosis in diabetic albino rats: a histological and immunohistochemical study. Benha Med. J., 2018, 35(3), 378.
[http://dx.doi.org/10.4103/bmfj.bmfj_122_18]
[24]
Yang, R.; Jia, Q.; Liu, X.F.; Ma, S.F. Effect of genistein on myocardial fibrosis in diabetic rats and its mechanism. Mol. Med. Rep., 2018, 17(2), 2929-2936.
[PMID: 29257312]
[25]
Nunes, S.; Rolo, A.P.; Palmeira, C.M.; Reis, F. Diabetic Cardiomyopathy: Focus on Oxidative Stress, Mitochondrial Dysfunction and Inflammation. In: Cardiomyopathies-Types and Treatments; InTech, 2017.
[26]
Sharma, P.; Jha, A. B.; Dubey, R. S.; Pessarakli, M. Reactive oxygen species, oxidative damage, and antioxidative defense mechanism in plants under stressful conditions., 2012.
[http://dx.doi.org/10.1155/2012/217037]
[27]
Ni, R.; Cao, T.; Xiong, S.; Ma, J.; Fan, G-C.; Lacefield, J.C.; Lu, Y.; Le Tissier, S.; Peng, T. Therapeutic inhibition of mitochondrial reactive oxygen species with mito-TEMPO reduces diabetic cardiomyopathy. Free Radic. Biol. Med., 2016, 90, 12-23.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.11.013] [PMID: 26577173]
[28]
Huda, S.; Akhter, N. Modulation of oxidative stress by enalapril and valsartan in adrenaline treated rats: a comparative study. Bangladesh Med. Res. Counc. Bull., 2014, 40(1), 25-30.
[http://dx.doi.org/10.3329/bmrcb.v40i1.20333] [PMID: 26118169]
[29]
Wang, X.; Tao, Y.; Huang, Y.; Zhan, K.; Xue, M.; Wang, Y.; Ruan, D.; Liang, Y.; Huang, X.; Lin, J.; Chen, Z.; Lv, L.; Li, S.; Chen, G.; Wang, Y.; Chen, R.; Cong, W.; Jin, L. Catalase ameliorates diabetes-induced cardiac injury through reduced p65/RelA- mediated transcription of BECN1. J. Cell. Mol. Med., 2017, 21(12), 3420-3434.
[http://dx.doi.org/10.1111/jcmm.13252] [PMID: 28643395]
[30]
Yang, R.; Jia, Q.; Liu, X.; Gao, Q.; Wang, L.; Ma, S. Effect of hydrogen sulfide on oxidative stress and endoplasmic reticulum stress in diabetic cardiomyopathy., 2016.
[31]
Wilson, A.J.; Gill, E.K.; Abudalo, R.A.; Edgar, K.S.; Watson, C.J.; Grieve, D.J. Reactive oxygen species signalling in the diabetic heart: emerging prospect for therapeutic targeting. Heart, 2018, 104(4), 293-299.
[PMID: 28954833]
[32]
Amirkhizi, F.; Siassi, F.; Minaie, S.; Djalali, M.; Rahimi, A.; Chamari, M. Is obesity associated with increased plasma lipid peroxidation and oxidative stress in women? ARYA Atheroscler., 2010, 2(4)
[33]
Saravanan, R.; Pari, L. Effect of a novel insulinotropic agent, succinic acid monoethyl ester, on lipids and lipoproteins levels in rats with streptozotocin-nicotinamide-induced type 2 diabetes. J. Biosci., 2006, 31(5), 581-587.
[http://dx.doi.org/10.1007/BF02708410] [PMID: 17301496]
[34]
Saravanan, G.; Ponmurugan, P. Ameliorative potential of Sallylcysteine: effect on lipid profile and changes in tissue fatty acid composition in experimental diabetes. Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie 2012, 64(6), 639-44.
[35]
Zhang, L.; Keung, W.; Samokhvalov, V.; Wang, W.; Lopaschuk, G.D. Role of fatty acid uptake and fatty acid β-oxidation in mediating insulin resistance in heart and skeletal muscle. Biochim. Biophys. Acta, 2010, 1801(1), 1-22.
[http://dx.doi.org/10.1016/j.bbalip.2009.09.014] [PMID: 19782765]
[36]
Otake, H.; Suzuki, H.; Honda, T.; Maruyama, Y. Influences of autonomic nervous system on atrial arrhythmogenic substrates and the incidence of atrial fibrillation in diabetic heart. Int. Heart J., 2009, 50(5), 627-641.
[http://dx.doi.org/10.1536/ihj.50.627] [PMID: 19809211]
[37]
Bakovic, M.; Filipovic, N.; Ferhatovic Hamzic, L.; Kunac, N.; Zdrilic, E.; Vitlov Uljevic, M.; Kostic, S.; Puljak, L.; Vukojevic, K. Changes in neurofilament 200 and tyrosine hydroxylase expression in the cardiac innervation of diabetic rats during aging. Cardiovasc. Pathol., 2018, 32, 38-43.
[http://dx.doi.org/10.1016/j.carpath.2017.11.003] [PMID: 29175663]
[38]
Thaung, H.P.; Baldi, J.C.; Wang, H-Y.; Hughes, G.; Cook, R.F.; Bussey, C.T.; Sheard, P.W.; Bahn, A.; Jones, P.P.; Schwenke, D.O.; Lamberts, R.R. Increased efferent cardiac sympathetic nerve activity and defective intrinsic heart rate regulation in type 2 diabetes. Diabetes, 2015, 64(8), 2944-2956.
[http://dx.doi.org/10.2337/db14-0955] [PMID: 25784543]
[39]
Kuncová, J.; Svíglerová, J.; Tonar, Z.; Slavíková, J. Heterogenous changes in neuropeptide Y, norepinephrine and epinephrine concentrations in the hearts of diabetic rats. Auton. Neurosci., 2005, 121(1-2), 7-15.
[http://dx.doi.org/10.1016/j.autneu.2005.05.005] [PMID: 15955747]
[40]
Haas, A.V.; McDonnell, M.E. Pathogenesis of Cardiovascular Disease in Diabetes. Endocrinol. Metab. Clin. North Am., 2018, 47(1), 51-63.
[http://dx.doi.org/10.1016/j.ecl.2017.10.010] [PMID: 29407056]
[41]
Dimitropoulos, G.; Tahrani, A.A.; Stevens, M.J. Cardiac autonomic neuropathy in patients with diabetes mellitus. World J. Diabetes, 2014, 5(1), 17-39.
[http://dx.doi.org/10.4239/wjd.v5.i1.17] [PMID: 24567799]
[42]
Pop-Busui, R.; Kirkwood, I.; Schmid, H.; Marinescu, V.; Schroeder, J.; Larkin, D.; Yamada, E.; Raffel, D.M.; Stevens, M.J. Sympathetic dysfunction in type 1 diabetes: association with impaired myocardial blood flow reserve and diastolic dysfunction. J. Am. Coll. Cardiol., 2004, 44(12), 2368-2374.
[http://dx.doi.org/10.1016/j.jacc.2004.09.033] [PMID: 15607400]
[43]
Ravic, M.; Jakovljevic, V.; Ristic, P.; Srejovic, I.; Vranic, A.; Babic, G.; Bolevich, S. The Effects of Valsartan on Cardiac Function and Pro-Oxidative Parameters in the Streptozotocin-Induced Diabetic Rat Heart. Serb. J. Exp. Clin. Res., 2018.
[http://dx.doi.org/10.2478/sjecr-2018-0049]
[44]
Seeger, H.; Lippert, C.; Wallwiener, D.; Mueck, A.O. Valsartan and candesartan can inhibit deteriorating effects of angiotensin II on coronary endothelial function. J. Renin Angiotensin Aldosterone Syst., 2001, 2(2), 141-143.
[http://dx.doi.org/10.3317/jraas.2001.016] [PMID: 11881114]
[45]
Sukumaran, V.; Tsuchimochi, H.; Tatsumi, E.; Shirai, M.; Pearson, J.T. Azilsartan ameliorates diabetic cardiomyopathy in young db/db mice through the modulation of ACE-2/ANG 1-7/Mas receptor cascade. Biochem. Pharmacol., 2017, 144, 90-99.
[http://dx.doi.org/10.1016/j.bcp.2017.07.022] [PMID: 28789938]
[46]
Ferrario, C.M.; Jessup, J.; Chappell, M.C.; Averill, D.B.; Brosnihan, K.B.; Tallant, E.A.; Diz, D.I.; Gallagher, P.E. Effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2. Circulation, 2005, 111(20), 2605-2610.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.104.510461] [PMID: 15897343]
[47]
Fogari, R.; Zoppi, A.; Maffioli, P.; Monti, C.; Lazzari, P.; Mugellini, A.; Derosa, G. Effects of aliskiren on QT duration and dispersion in hypertensive patients with type 2 diabetes mellitus. Diabetes Obes. Metab., 2012, 14(4), 341-347.
[http://dx.doi.org/10.1111/j.1463-1326.2011.01535.x] [PMID: 22074122]
[48]
Deano, R.; Sorrentino, M. Lipid effects of antihypertensive medications. Curr. Atheroscler. Rep., 2012, 14(1), 70-77.
[http://dx.doi.org/10.1007/s11883-011-0214-z] [PMID: 22037772]
[49]
Tabbi-Anneni, I.; Buchanan, J.; Cooksey, R.C.; Abel, E.D. Captopril normalizes insulin signaling and insulin-regulated substrate metabolism in obese (ob/ob) mouse hearts. Endocrinology, 2008, 149(8), 4043-4050.
[http://dx.doi.org/10.1210/en.2007-1646] [PMID: 18450963]
[50]
Perlstein, T.S.; Henry, R.R.; Mather, K.J.; Rickels, M.R.; Abate, N.I.; Grundy, S.M.; Mai, Y.; Albu, J.B.; Marks, J.B.; Pool, J.L.; Creager, M.A. Effect of angiotensin receptor blockade on insulin sensitivity and endothelial function in abdominally obese hypertensive patients with impaired fasting glucose. Clin. Sci. (Lond.), 2012, 122(4), 193-202.
[http://dx.doi.org/10.1042/CS20110284] [PMID: 21861845]
[51]
Martín-Timón, I.; Sevillano-Collantes, C.; Marín-Peñalver, J.J.; del Cañizo-Gómez, F.J. MANAGEMENT OF CARDIOVASCULAR RISK FACTORS IN TYPE 2 DIABETES MELLITUS PATIENTS. EMJ, 2016, 1(4), 89-97.
[52]
Kitamura, N.; Takahashi, Y.; Yamadate, S.; Asai, S. Angiotensin II receptor blockers decreased blood glucose levels: a longitudinal survey using data from electronic medical records. Cardiovasc. Diabetol., 2007, 6(1), 26.
[http://dx.doi.org/10.1186/1475-2840-6-26] [PMID: 17903269]
[53]
Fujimoto, M.; Masuzaki, H.; Tanaka, T.; Yasue, S.; Tomita, T.; Okazawa, K.; Fujikura, J.; Chusho, H.; Ebihara, K.; Hayashi, T.; Hosoda, K.; Nakao, K. An angiotensin II AT1 receptor antagonist, telmisartan augments glucose uptake and GLUT4 protein expression in 3T3-L1 adipocytes. FEBS Lett., 2004, 576(3), 492-497.
[http://dx.doi.org/10.1016/j.febslet.2004.09.027] [PMID: 15498586]
[54]
Ciccarelli, L. Angiotensin II receptor blockers and insulin resistance. Hypertens. Res., 2010, 33(8), 779.
[http://dx.doi.org/10.1038/hr.2010.99] [PMID: 20535122]
[55]
Chhabra, K.H.; Chodavarapu, H.; Lazartigues, E. Angiotensin converting enzyme 2: a new important player in the regulation of glycemia. IUBMB Life, 2013, 65(9), 731-738.
[http://dx.doi.org/10.1002/iub.1190] [PMID: 23893738]
[56]
Derosa, G.; Ragonesi, P.D.; Mugellini, A.; Ciccarelli, L.; Fogari, R. Effects of telmisartan compared with eprosartan on blood pressure control, glucose metabolism and lipid profile in hypertensive, type 2 diabetic patients: a randomized, double-blind, placebo-controlled 12-month study. Hypertens. Res., 2004, 27(7), 457-464.
[http://dx.doi.org/10.1291/hypres.27.457] [PMID: 15302981]
[57]
Kasiske, B.L.; Ma, J.Z.; Kalil, R.S.; Louis, T.A. Effects of antihypertensive therapy on serum lipids. Ann. Intern. Med., 1995, 122(2), 133-141.
[http://dx.doi.org/10.7326/0003-4819-122-2-199501150-00010] [PMID: 7992988]
[58]
McFarlane, S.I.; Kumar, A.; Sowers, J.R. Mechanisms by which angiotensin-converting enzyme inhibitors prevent diabetes and cardiovascular disease. Am. J. Cardiol., 2003, 91(12A), 30H-37H.
[http://dx.doi.org/10.1016/S0002-9149(03)00432-6] [PMID: 12818733]
[59]
Scheen, A.J. Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 1. A meta-analysis of randomised clinical trials. Diabetes Metab., 2004, 30(6), 487-496.
[http://dx.doi.org/10.1016/S1262-3636(07)70146-5] [PMID: 15671918]
[60]
Bayorh, M.A.; Ganafa, A.A.; Socci, R.R.; Eatman, D.; Silvestrov, N.; Abukhalaf, I.K. Effect of losartan on oxidative stress-induced hypertension in Sprague-Dawley rats. Am. J. Hypertens., 2003, 16(5 Pt 1), 387-392.
[http://dx.doi.org/10.1016/S0895-7061(03)00054-2] [PMID: 12745201]
[61]
Kim, H.J.; Han, S.J.; Kim, D.J.; Jang, H.C.; Lim, S.; Choi, S.H.; Kim, Y.H.; Shin, D.H.; Kim, S.H.; Kim, T.H.; Ahn, Y.B.; Ko, S.H.; Kim, N.H.; Seo, J.A.; Kim, H.Y.; Lee, K.W. Effects of valsartan and amlodipine on oxidative stress in type 2 diabetic patients with hypertension: a randomized, multicenter study. Korean J. Intern. Med. (Korean. Assoc. Intern. Med.), 2017, 32(3), 497-504.
[http://dx.doi.org/10.3904/kjim.2015.404] [PMID: 28490725]
[62]
Birben, E.; Sahiner, U.M.; Sackesen, C.; Erzurum, S.; Kalayci, O. Oxidative stress and antioxidant defense. World Allergy Organ. J., 2012, 5(1), 9-19.
[http://dx.doi.org/10.1097/WOX.0b013e3182439613] [PMID: 23268465]

Rights & Permissions Print Cite
Article Metrics
12
1
1
© 2024 Bentham Science Publishers | Privacy Policy