Resveratrol Suppresses Cardiac Renin Angiotensin System in the Late Phase of Left Ventricular Hypertrophy

Document Type: Original paper

Authors

1 Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

2 Yazd Cardiovascular Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

3 Department of Biochemistry, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

4 School of Veterinary Medicine, Shiraz University, Shiraz, Iran.

5 Department of Physiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.Biotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.

Abstract

Background and objectives: Resveratrol(3,5,4′-trihydroxy-trans-stilbene) is a natural polyphenole phytoalexin which exerts potential cardioprotective effects, but the cellular and molecular mechanisms responsible for these effects are still unknown. Cardiac renin angiotensin system (RAS) over-activation plays an important role in pathogenesis of left ventricular hypertrophy (LVH) progression. The aim of the study was to investigate the effects of resveratrol on the main components of RAS during early and late phase of myocardial hypertrophy. Methods: To consider the early and late phase of LVH, the rats were studied two and sixteen weeks after abdominal aorta banding without treatment (H2w and H16w groups, respectively) or with resveratrol (R) treatment. Intact animals served as control (Ctl). Arterial blood pressure was recorded by carotid cannulation. Angiotensin II (Ang II) level was measured using ELISA kit. Gene expression was evaluated by Real time RT-PCR technique. Cardiomyocyte size and fibrosis were assessed using haematoxylin/eosin and Masson trichrome staining, respectively Results: Results of this study showed that in H2w group AT1a mRNA level was increased significantly (pConclusion: Progression of LVH is accompanied by dynamic changes in RAS components expression in myocardial tissue. Resveratrol protects the heart against pressure overload-induced hypertrophy in part via RAS suppression.

Keywords


[1] Kuschnir E. The left ventricle and hemodynamic patterns in essential hypertension. Regul Pept. 2005; 128(3): 221-225.

[2] Kokubo Y, Matsumoto C. Hypertension is a risk factor for several types of heart disease. Adv Exp Med Biol. 2017; 956: 419-426.

[3] Hill JAOlson EN. Cardiac plasticity. N Engl J Med. 2008; 358(13): 1370-1380.

[4] Garcia JA, Incerpi EK. Factors and mechanisms involved in left ventricular hypertrophy and the anti-hypertrophic role of nitric oxide. Arq Bras Cardiol. 2008; 90(6): 409-416.

[5] Verbrugge FH, Tang WH, Mullens W. Renin-Angiotensin-aldosterone system activation during decongestion in acute heart failure: friend or foe? JACC Heart Fail. 2015; 3(2): 108-111.

[6] Muñoz-Durango N, Fuentes CA, Castillo AE, González-Gómez LM, Vecchiola A, Fardella CE, Kalergis AM. Role of the renin-angiotensin-aldosterone system beyond blood pressure regulation: molecular and cellular mechanisms involved in end-organ damage during arterial hypertension. Int J Mol Sci. 2016; 17(7): 1-17.

[7] SimMK, Chen WS. Effects of losartan on angiotensin receptors in the hypertrophic rat heart. Reg Pept. 2006; 137(3): 140-146.

[8] De Mello WC, Frohlich ED.Clinical perspectives and fundamental aspects of local cardiovascular and renal renin-angiotensin systems. Front Endocrinol. 2014; 5: 1-9.

[9] Huggins CE, Domenighetti AA, Pedrazzini T, Pepe S, Delbridge LM. Elevated intracardiac angiotensin II leads to cardiac hypertrophy and mechanical dysfunction in normotensive mice. J Renin Angiotensin Aldosterone Syst. 2003; 4(3): 186-190.

[10] Brilla CG, Funck RC, Rupp H. Lisinopril-mediated regression of myocardial fibrosis in patients with hypertensive heart disease. Circulation. 2000; 102(12): 1388-1393.

[11] Dahlöf B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H. LIFE Study Group. Cardiovascular morbidity and mortality in the losartan intervention for endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002; 359(9311): 995-1003.

[13] Safari F, Bayat G, Shekarforoush S, Hekmatimoghaddam S, Anvari Z, Moghadam MF, Hajizadeh S.  Expressional profile of cardiac uncoupling protein-2 following myocardial ischemia reperfusion in losartan- and ramiprilat-treated rats. J Renin Angiotensin Aldosterone Syst. 2014; 15(3): 209-217.

[14] Dasgupta C, Zhang L. Angiotensin II receptors and drug discovery in cardiovascular disease. Drug Discov Today. 2011; 16(1-2): 22-34.

[15] Seshiah PN, Weber DS, Rocic P, Valppu L, Taniyama Y, Griendling KK.  Angiotensin II stimulation of NAD(P)H oxidase activity: upstream mediators. Circ Res. 2002; 91(5): 406-413.

[16] Kupfahl C, Pink D, Friedrich K, Zurbrügg HR, Neuss M, Warnecke C, Fielitz J, Graf K, Fleck E, Regitz-Zagrosek V. Angiotensin II directly increases transforming growth factor beta1 and osteopontin and indirectly affects collagen mRNA expression in the human heart. Cardiovasc Res. 2000; 46(3): 463-475.

[17] Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006; 5(6): 493-506.

[18] Dolinsky VW, Chakrabarti S, Pereira TJ, Oka T, Levasseur J, Beker D, Zordoky BN, Morton JS, Nagendran J, Lopaschuk GD, Davidge ST, Dyck JR. Resveratrol prevents hypertension and cardiac hypertrophy in hypertensive rats and mice. Biochim Biophys Acta. 2013; 1832(10): 1723-1733.

[19] Lin Y, Zhu J, Zhang X, Wang J, Xiao W, Li B, Jin L, Lian J, Zhou L, Liu J. Inhibition of cardiomyocytes hypertrophy by resveratrol is associated with amelioration of endoplasmic reticulum stress. Cell Physiol Biochem. 2016; 39(2): 780-789.

[20] Fan Y, Liu L, Fang K, Huang T, Wan L, Liu Y, Zhang S, Yan D, Li G, Gao Y, Lv Y, Chen Y, Tu Y. Resveratrol ameliorates cardiac hypertrophy by down-regulation of miR-155 through activation of breast cancer type 1 susceptibility protein. J Am Heart Assoc. 2016; Article ID e002648.

[21] Yang L, Zhang Y, Zhu M, Zhang Q, Wang X, Wang Y, Zhang J, Li J, Yang L, Liu J, Liu F, Yang Y, Kang L, Shen Y, Qi Z. Resveratrol attenuates myocardial ischemia/reperfusion injury through up-regulation of vascular endothelial growth factor B. Free Radic Biol Med. 2016; 101: 1-9.

[22] Messina F, Guglielmini G, Curini M, Orsini S, Gresele P, Marcotullio MC. Effect of substituted stilbenes on platelet function. Fitoterapia. 2015; 105: 228-233.

[23] Dorri Mashhadi F, Zavvar Reza J, Jamhiri M, Hafizi Z, Zare Mehrjardi F, Safari F. The effect of resveratrol on angiotensin II levels and the rate of transcription of its receptors in the rat cardiac hypertrophy model. J Physiol Sci. 2016; 67(2): 303-309.

[24] Busk PK, Bartkova J, Strøm CC, Wulf-Andersen L, Hinrichsen R, Christoffersen TE, Latella L, Bartek J, Haunsø S, Sheikh SP. Involvement of cyclin D activity in left ventricle hypertrophy in vivo and in vitro. Cardiovasc Res. 2002; 56(1): 64-75.

[25] Doggrell SA, Brown L. Rat models of hypertension, cardiac hypertrophy and failure. Cardiovasc Res.1998; 39(1): 89-105.

[26] Wojciechowski P, Juric D, Louis XL, Thandapilly SJ, Yu L, Taylor C, Netticadan T. Resveratrol arrests and regresses the development of pressure overload- but not volume overload-induced cardiac hypertrophy in rats. J Nutr. 2010; 140(5): 962-968.

[27] Thandapilly SJ, Wojciechowski P, Behbahani J, Louis XL, Yu L, Juric D, Kopilas MA, Anderson HD, Netticadan T. Resveratrol prevents the development of pathological cardiac hypertrophy and contractile dysfunction in the SHR without lowering blood pressure. Am J Hypertens. 2010; 23(2): 192-196.

[28] Sakatani T, Shirayama T, Yamamoto T, Mani H, Shiraishi H, Matsubara H. Cardiac hypertrophy diminished the effects of isoproterenol on delayed rectifier potassium current in rat heart. J Physiol Sci. 2006; 56(2): 173-181.

[29] Rao X, Huang X, Zhou Z, Lin X.  An improvement of the 2ˆ(-delta delta CT) method for quantitative real-time polymerase chain reaction data analysis. Biostat Bioinforma Biomath. 2013; 3(3): 71-85.

[30] Arya SS, Salve AR, Chauhan S. Peanuts as functional food: a review. J Food Sci Technol. 2016; 53(1): 31-41.

[31] Burns J, Yokota T, Ashihara H, Lean ME, Crozier A. Plant foods and herbal sources of resveratrol. J Agric Food Chem. 2002; 50(11): 3337-3340.

[32] Dolinsky VW, Soltys CL, Rogan KJ, Chan AY, Nagendran J, Wang S, Dyck JR. Resveratrol prevents pathological but not physiological cardiac hypertrophy. J Mol Med. 2015; 93(4): 413-425.

[33] Chan AY, Dolinsky VW, Soltys CL, Viollet B, Baksh S, Light PE, Dyck JR. Resveratrol inhibits cardiac hypertrophy viaAMP-activated protein kinase and Akt. J Biol Chem.2008; 283(35): 24194-24201.

[34] Safari F, Shekarforoosh S, Hashemi T, Namvar Aghdash S, Fekri A, Safari F.  Sirtinol abrogates late phase of cardiac ischemia preconditioning in rats. J Physiol Sci. 2016; 67(4): 515-522.

[35] Sundaresan NR, Pillai VB, Gupta MP. Emergingroles of SIRT1 deacetylase in regulating cardiomyocyte survival and hypertrophy. J Mol Cell Cardiol. 2011; 51(4): 614-618.

[36] Juric D, Wojciechowski P, Das DK, Netticadan T.  Prevention of concentric hypertrophy and diastolic impairment in aortic-banded rats treated with resveratrol. Am J Physiol Heart Circ Physiol. 2007; 292(5): 2138-2143.

[37] Burstein B, Maguy A, Clément R, Gosselin H, Poulin F, Ethier N, Tardif JC, Hébert TE, Calderone A, Nattel S. Effects of resveratrol (trans-3,5,4'-trihydroxystilbene) treatment on cardiac remodeling following myocardial infarction. J Pharmacol Exp Ther. 2007; 323(3): 916-923.

[38] Safari F, Zarei F, Shekarforoush S, Fekri A, Klishadi MS, Hekmatimoghaddam S. Combined 1,25-dihydroxy-vitamin D and resveratrol: a novel therapeutic approach to ameliorate ischemia reperfusion-induced myocardial injury. Int J Vitam Nutr Res. 2015; 85(3-4): 174-184.

[39] Paul M, Poyan Mehr A, Kreutz R. Physiology of local renin-angiotensin systems. Physiol Rev. 2006; 86(3): 747-803.

[40] Wollert KC, Drexler H. The renin-angiotensin system and experimentalheart failure. Cardiovasc Res. 1999; 43(4): 838-849.

[41] Schultz Jel J, Witt SA, Glascock BJ, Nieman ML, Reiser PJ, Nix SL, Kimball TR, Doetschman T. TGF-beta1mediates the hypertrophic cardiomyocyte growth induced by angiotensin II. J Clin Invest. 2002; 109(6): 787-796.

[42] Sadoshima J, Xu Y, Slayter HS, Izumo S. Autocrinerelease of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell. 1993; 75(5): 977-984.

[43] Paradis P, Dali-Youcef N, Paradis FW, Thibault G, Nemer M. Overexpression of angiotensin II type I receptor in cardiomyocytes induces cardiac hypertrophy and remodeling. Proc Natl Acad Sci USA. 2000; 97(2): 931-936.

[44] Lambert C, Massillon Y, Meloche S. Upregulation of cardiac angiotensin II AT1 receptors in congenital cardiomyopathic hamsters. Circ Res. 1995; 77(5): 1001-1007.

[45] Van Esch JH, Gembardt F, Sterner-Kock A, Heringer-Walther S, Le TH, Lassner D, Stijnen T, Coffman TM, Schultheiss HP, Danser AH, Walther T. Cardiacphenotype and angiotensin II levels in AT1a, AT1b, and AT2 receptor single, double, and triple knockouts. Cardiovasc Res. 2010; 86(3): 401-409.

[46] D'Amore A, Black MJ, Thomas WG. The angiotensin II type 2 receptor causes constitutive growth of cardiomyocytes and does not antagonize angiotensin II type 1 receptor-mediated hypertrophy. Hypertension. 2005; 46(6): 1347-1354.

[47] Adachi Y, Saito Y, Kishimoto I, Harada M, Kuwahara K, Takahashi N, Kawakami R, Nakanishi M, Nakagawa Y, Tanimoto K, Saitoh Y, Yasuno S, Usami S, Iwai M, Horiuchi M, Nakao K. Angiotensin II type2 receptord eficiency exacerbates heart failure and reduces survival after acute myocardial infarction in mice. Circulation. 2003; 107(19): 2406-2408.

[48] Kurabayashi M, Yazaki Y. Downregulation of angiotensin II receptortype1 in heart failure. A process of adaptation or deterioration? Circulation.1997; 95(5): 1104-1107.

[49] Suzuki J, Matsubara H, Urakami M, Inada M. Rat angiotensin II (type1A) receptor mRNA regulation and subtype expression in myocardial growth and hypertrophy. Circ Res. 1993; 73(3): 439-447.

[50] Nio Y, Matsubara H, Murasawa S, Kanasaki M, Inada M. Regulation of gene transcription of angiotensin II receptor subtypes in myocardial infarction. J Clin Invest. 1995; 95(1): 46-54.

[51] Iwai N, Shimoike H, Kinoshita M. Cardiac renin-angiotensin system in the hypertrophied heart. Circulation. 1995; 92(9): 2690-2696.

[52] Schultz D, Su X, Wei CC, Bishop SP, Powell P, Hankes GH, Dillon AR, Rynders P, Spinale FG, Walcott G, Ideker R, Dell'Italia LJ. Downregulation of ANGII receptor is associated with compensated pressure-overload hypertrophy in the young dog. Am J Physiol Heart Circ Physiol. 2002; 282(2): 749-756.

[53] Danser AH, van Kesteren CA, Bax WA, Tavenier M, Derkx FH, Saxena PR, Schalekamp MA. Prorenin, renin, angiotensinogen,and angiotensinconverting enzyme in normal and failing humanhearts.  Evidence for renin binding. Circulation. 1997; 96(1): 220-226.

[54] Passier RC, Smits JF, Verluyten MJ, Daemen MJ. Expression and localization of renin and angiotensinogen in rat heart after myocardial infarction. Am J Physiol. 1996; 271(3): 1040-10488.

[55] Ichiki T, Miyazaki R, Kamiharaguchi A, Hashimoto T, Matsuura H, Kitamoto S, Tokunou T, Sunagawa K. Resveratrol attenuates angiotensin II-induced senescence of vascular smooth muscle cells. Regul Pept. 2012; 177(1-3): 35-39.