Horm Metab Res 2015; 47(07): 521-527
DOI: 10.1055/s-0034-1394373
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Fructose-Rich Diet-Induced Changes in the Expression of the Renin Angiotensin System Molecules in the Heart of Ovariectomized Female Rats Could be Reversed by Estradiol

M. Bundalo
1   Laboratory for Radiobiology and Molecular Genetics, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia
,
M. Zivkovic
1   Laboratory for Radiobiology and Molecular Genetics, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia
,
S. Tepavcevic
2   Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia
,
T. Culafic
2   Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia
,
G. Koricanac
2   Laboratory for Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia
,
A. Stankovic
1   Laboratory for Radiobiology and Molecular Genetics, Vinca Institute of Nuclear Sciences, University of Belgrade, Belgrade, Serbia
› Author Affiliations
Further Information

Publication History

received 16 July 2014

accepted 24 September 2014

Publication Date:
04 November 2014 (online)

Abstract

The renin-angiotensin system has been implicated in the development of metabolic syndrome and appears to be a key in the local tissue control of normal cardiac functions. Physiological concentrations of estrogens have been shown to be cardioprotective, especially against the damaging effects of fructose-rich diet. The aim of the study was to investigate the expression of the renin-angiotensin system molecules with potentially deleterious effect on the heart (angiotensin-converting enzyme and angiotensin II type 1 receptor) and those with potentially protective effects, (angiotensin-converting enzyme 2 and angiotensin II type 2 receptor), in ovariectomized fructose fed female rats with 17β-estradiol replacement. Real-time PCR and Western blot analysis were used for quantification of gene and protein expression in the heart. Fructose diet increased the expression of angiotensin-converting enzyme and angiotensin II type 1 receptor and decreased the expression of angiotensin-converting enzyme 2 and angiotensin II type 2 receptor. On the other hand, estradiol replacement seems to undo fructose diet effects on cardiac renin-angiotensin system. Downregulation of angiotensin-converting enzyme and angiotensin II type 1 receptor, and reversion of expression of both potentially protective molecules, angiotensin-converting enzyme 2 and angiotensin II type 2 receptor, to the control level in cardiac tissue took place. Obtained results suggest that estradiol may reverse the harmful effect of fructose-rich diet on the expression of renin-angiotensin system molecules. These findings may also be important in further research of phenotypes like insulin resistance, metabolic syndrome, and following cardiovascular pathology in females.

 
  • References

  • 1 Tran LT, Yuen VG, McNeill JH. The fructose fed rat: a review of the mechanism of fructose-induced insulin resistance and hypertension. Mol Cell Biochem 2009; 332: 145-159
  • 2 Wu K, Hung CY, Chan J, Wu C. An increase in adenosine-5′-triphosphate (ATP) content in rostral ventrolateral medulla is engaged in the high fructose diet-induced hypertension. J Biomed Sci 2014; 21: 8
  • 3 Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005; 365: 1415-1428
  • 4 Patten RD, Karas RH. Estrogen replacement and cardiomyocyte protection. Trends Cardiovasc Med 2006; 16: 69-75
  • 5 Galipeau D, Verma S, McNeill JH. Female rats are protected against fructose-induced changes in metabolism and blood pressure. Am J Physiol Heart Circ Physiol 2002; 283: H2478-H2484
  • 6 Danser J, Saris J, Schuijt M, van Kat J. Is there a local renin-angiotensin system in the heart?. Cardiovasc Res 1999; 44: 252-265
  • 7 Paul M, Mehr AP, Kreutz AR. Physiology of Local Renin-Angiotensin Systems. Physiol Rev 2006; 86: 747-803
  • 8 Cooper SA, Whaley-Connell A, Habibi J, Wei Y, Lastra G, Manrique C, Stas S, Sowers JR. Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance. Am J Physiol Heart Circ Physiol 2007; 293: H2009-H2023
  • 9 Nyby M, Abedi K, Smutko V, Eslami P, Tuck M. Vascular Angiotensin Type 1 Receptor Expression Is Associated with Vascular Dysfunction, Oxidative Stress and Inflammation in Fructose-Fed Rats. Hypertens Res 2007; 30: 451-457
  • 10 Nickenig G, Baumer AT, Grohe C, Kahlert S, Strehlow K, Rosenkranz S, Stablein A, Beckers F, Smits JF, Daemen MJ, Bohm M. Estrogen modulates AT1 receptor gene expression in vitro and in vivo. Circulation 1998; 97: 2197-2201
  • 11 Tanaka M, Nakaya S, Watanbe M, Kumai T, Tateishi T, Kobayashi S. Effects of ovariectomy and estrogen replacement on aorta angiotensin-converting enzyme activity in rats. Jpn J Pharmacol 1997; 73: 361-363
  • 12 Dean SA, Tan J, O’Brien ER, Leenen FH. 17beta-estradiol down regulates tissue angiotensin-converting enzyme and ANG II type 1 receptor in female rats. Am J Physiol Regul Integr Comp Physiol 2005; 288: R759-R766
  • 13 Sales S, Ureshino RP, Pereira RT, Luna MS, Pires de Oliveira M, Yamanouye N, Godinho RO, Smaili SS, Porto CS, Abdalla FM. Effects of 17beta-estradiol replacement on the apoptotic effects caused by ovariectomy in the rat hippocampus. Life Sci 2010; 86: 832-838
  • 14 Koricanac G, Milosavljevic T, Stojiljkovic M, Zakula Z, Tepavcevic S, Ribarac-Stepic N, Isenovic ER. Impact of estradiol on insulin signaling in the rat heart. Cell Biochem Funct 2009; 27: 102-110
  • 15 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
  • 16 Korićanac G, Djordjević A, Žakula Z, Vojnović-Milutinović D, Tepavčević S, Veličković N, Milosavljević T, Stojiljković M, Romić S, Matić G. Gender modulates development of the metabolic syndrome phenotype in fructose fed rats. Arch Biol Sci 2013; 65: 455-464
  • 17 Romic S, Tepavcevic S, Zakula Z, Milosavljevic T, Stojiljkovic M, Popovic M, Stankovic A, Koricanac G. Does oestradiol attenuate the damaging effects of a fructose-rich diet on cardiac Akt/endothelial nitric oxide synthase signaling?. Br J Nutr 2013; 109: 1940-1948
  • 18 Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25: 402-408
  • 19 Benicky J, Hafko R, Sanchez-Lemus E, Aguilera G, Saavedra JM. Six commercially available angiotensin II AT1receptor antibodies are non-specific. Cell Mol Neurobiol 2012; 32: 1353-1365
  • 20 Fukui T, Hirano T, Shiraishi Y, Nagashima M, Adachi M. Chronic insulin infusion normalizes blood pressure and the gene expressions of angiotensin II type 1 receptor in fructose-fed rats. Hypertens Res 2008; 31: 127-133
  • 21 Wassmann S, Nickenig G. Pathophysiological regulation of the AT1-receptor and implications for vascular disease. J Hypertens Suppl 2006; 24: S15-S21
  • 22 Giani JF, Muñoz MC, Mayer MA, Veiras LC, Arranz C, Taira CA, Turyn D, Toblli JE, Dominici FP. Angiotensin-(1–7) improves cardiac remodeling and inhibits growth-promoting pathways in the heart of fructose fed rats. Am J Physiol Heart Circ Physiol 2010; 298: H1003-H1013
  • 23 Zakula Z, Koricanac G, Tepavcevic S, Stoiljkovic M, Milosavljevic T, Isenovic ER. Impairment of cardiac insulin signaling in fructose-fed ovariectomized female Wistar rats. Eur J Nutr 2011; 50: 543-551
  • 24 Ng KK, Vane JR. Conversion of angiotensin I to angiotensin II. Nature 1967; 25: 762-766
  • 25 Corvol P, Michaud A, Soubrier F, Williams TA. Recent advances in knowledge of the structure and function of the angiotensin I converting enzyme. J Hypertens Suppl 1995; 13: S3-S10
  • 26 Wei Y, Whaley-Connell AT, Chen K, Habibi J, Uptergrove GM, Clark SE, Stump C, Ferrario C, Sowers JR. NADPH oxidase contributes to vascular inflammation, insulin resistance, and remodeling in the transgenic (mRen2) rat. Hypertension 2007; 50: 384-391
  • 27 Andreozzi F, Laratta E, Sciacqua A, Perticone F, Sesti G. Angiotensin II impairs the insulin signaling pathway promoting production of nitric oxide by inducing phosphorylation of insulin receptor substrate-1 on Ser312 and Ser616 in human umbilical vein endothelial cells. Circ Res 2004; 94: 1211-1218
  • 28 Alfarano C, Sartiani L, Nediani C, Mannucci E, Mugelli A, Cerbai E, Raimondi L. Functional coupling of angiotensin II type 1 receptor with insulin resistance of energy substrate uptakes in immortalized cardiomyocytes (HL-1 cells). Br J Pharmacol 2008; 153: 907-914
  • 29 Koricanac G, Tepavcevic S, Romic S, Milosavljevic T, Stojiljkovic M, Zakula Z. Expression and cellular distribution of glucose transporters and alfa subunits of Na+/k+-ATPase in the heart of fructose-fed female rats: The role of estradiol. Horm Metab Res 2014; 46: 109-115
  • 30 Takeuchi K, Alexander RW, Nakamura Y, Tsujino T, Murphy TJ. Molecular structure and transcriptional function of the rat vascular AT1a angiotensin receptor gene. Circ Res 1993; 73: 612-621
  • 31 Wu Z, Maric C, Roesch D, Zheng W, Verbalis AG, Sandberg K. Estrogen regulates adrenal angiotensin AT1 receptors by modulating AT1 receptor translation. Endocrinology 2003; 144: 3251-3261
  • 32 Hsieh PS, Tai YH, Loh CH, Shih KC, Cheng WT, Chu CH. Functional interaction of AT1 and AT2 receptors in fructose-induced insulin resistance and hypertension in rats. Metabolism 2005; 54: 157-164
  • 33 Sohn HY, Raff U, Hoffmann A, Gloe T, Heermeier K, Galle J, Pohl U. Differential role of angiotensin II receptor subtypes on endothelial superoxide formation. Br J Pharmacol 2000; 131: 667-672
  • 34 Okumura M, Iwai M, Ide A, Mogi M, Ito M, Horiuchi M. Sex difference in vascular injury and vasoprotective effect of valsartan are related to differential AT2 receptor expression. Hypertension 2005; 46: 589-595
  • 35 Gross ML, Adamczak M, Rabe T, Harbi NA, Krtil J, Koch A, Hamar P, Amann K, Ritz E. Beneficial effects of estrogens on indices of renal damage in uninephrectomized SHRsp rats. J Am Soc Nephrol 2004; 15: 348-358
  • 36 Crackower MA, Sarao R, Oudit GY, Yagil C, Kozieradzki I, Scanga SE, Oliveira-dos-Santos AJ, da Cosat J, Zhang L, Pei Y, Scholey J, Ferrario CM, Manoukian AS, Chappell MC, Backx PH, Yagil Y, Penninger JM. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 2002; 417: 822-828
  • 37 Lautner RQ, Villela DC, Fraga-Silva RA, Silva N, Verano-Braga T, Costa-Fraga F, Jankowski J, Jankowski V, Sousa F, Alzamora A, Soares E, Barbosa C, Kjeldsen F, Oliveira A, Braga J, Savergnini S, Maia G, Peluso AB, Passos-Silva D, Ferreira A, Alves F, Martins A, Raizada M, Paula R, Motta-Santos D, Klempin F, Pimenta A, Alenina N, Sinisterra R, Bader M, Campagnole-Santos MJ, Santos RA. Discovery and characterisation of alamandine: a novel component of the renin-angiotensin system. Circ Res 2013; 112: 1104-1111
  • 38 Steckelings UM, Unger T. The renin-angiotensin-aldosterone system. In: Man Hypertens Eur Soc Hypertens. 1st ed. London: Inform Healthcare; 2008: 110-116