Antioxidant Protective Effects of the Resveratrol on the Cardiac and Vascular Tissues from Renal Hypertensive Rats

Joyce Cristina de Oliveira, Carla Renata Kitanish Antonietto, Angélica Cristina Scalabrini, Talita Sanches Marinho, Larissa Pernomian, José Wilson N. Corrêa, Carolina Baraldi Araujo Restini

Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences from Ribeir?o Preto, Laboratory of Pharmacology, University of S?o Paulo, Ribeir?o Preto, Brazil.
Federal University of Amazonas, Manaus, Brazil.
School of Medicine, Animal Experimental Laboratory, University of Ribeir?o Preto, Ribeir?o Preto, Brazil.
School of Nutrition, University of Ribeir?o Preto, Ribeir?o Preto, Brazil.
School of Pharmaceutical Sciences, University of Ribeir?o Preto, Ribeir?o Preto, Brazil.

DOI: 10.4236/ojmc.2012.23008                

Abstract

Background: Accumulating reactive oxygen species (ROS) is involved in cellular signaling and function disturbances due to the oxidative stress, which contributes to several diseases. The consequences of ROS activity represent an im-portant mechanism on the pathogenesis of vascular diseases, such as hypertension. Increased blood pressure observed in renal hypertension of the 2 kidneys-1 clip (2K-1C) model involves increased ROS levels in the cardiovascular system. Resveratrol, a polyphenolic compound primarily found in red wine, has many biological and pharmacological proper-ties. Considering the antioxidant properties of resveratrol, the present study was aimed to investigate the effects of the chronic treatment with resveratrol on cardiovascular system from renal hypertensive rats. Results: 2K-1C hypertension presented increased blood pressure, which was reduced at the end of the fifth week of resveratrol treatment. The cardiac hypertrophy index and the basal levels of ROS in rat aortic rings were also reduced by resveratrol treatment. Conclusions: The present findings clearly show the protective effects from resveratrol on the blood pressure, the car-diac growth and the vascular ROS generation in renal hypertension.

Keywords

Hypertension; Aorta; Superoxide; Resveratrol; Phenylephrine; Reactive Species of Oxygen (ROS)

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	M. Félétou and P. M. Vanhoutte, “Endothelial Dysfunction: A Multifaceted Disorder (The Wiggers Award Lecture),” The American Journal of Physiology (Heart and Circulatory Physiology), Vol. 291, No. 3, 2006, pp. H985-H1002.
[2]	R. M. Touyz, “Intracellular Mechanisms Involved in Vascular Remodelling of Resistance Arteries in Hypertension: Role of Angiotensin II,” Experimental Physiology, Vol. 90, No. 4, 2005, pp. 449-55.
[3]	R. Humar, L. Zimmerli and E. Battegay, “Angiogenesis and Hypertension: An Update,” J Hum Hypertension, Vol. 23, No. 12, 2009, pp. 773-782
[4]	M. Martinez-Maldonado, “Pathophysiology of Renovascular Hypertension,” Hypertension, Vol. 17, No. 5, 1991, pp. 707719.
[5]	H. Goldblatt, J. Lynch, R. F. Hanzal and W. W. Summerville, “Studies on Experimental Hypertension. The production of Persistent Elevation of Systolic Blood Pressure by Means of Renal Ischemia,” The Journal of Experimental Medicine, Vol. 59, No. 3, 1934, pp. 347-349.
[6]	C. M. Ferrario, “Importance of Rennin-AngiotensinAldosterone-System (RAS) in the Physiology and Pathology of Hyper-Tension,” Drugs, Vol. 39, Suppl. 2, 1990, pp. 1-8.
[7]	T. Heitzer, U. Wenzer, U. Hink, D. Krollner, M. Skatchkov, R. A. Stahl, R. MacHarzina, J. H. Br?sen, T. Meinertz and T. Münzel, “Increased NAD(P)H Oxidase Mediated Superoxide Production in Renovascular Hypertension Evidence for na Involvement of Protein Kinase C,” Kidney International, Vol. 55, No. 1, 1999, pp. 252-260.
[8]	L. O. Lerman, K. A. Nath, M. Rodriguez-Porcel, J. D. Krier, R. S. Schwartz, C. Napoli and J. C. Romero, “Increased Oxidative Stress in Experimental Renovascular Hypertension,” Hypertension, Vol. 37, No. 2, 2001, pp. 541-546.
[9]	Y. Higashi, S. Sasaki, K. Nakagawa, H. Matsuura, T. Oshima and K. Chayama, “Endothelial Function and Oxidative Stress in Renovascular Hypertension,” The New England Journal of Medicine, Vol. 346, No. 25, 2002, pp. 1954-1962.
[10]	C. Boulanger and T. F. Lüscher, “Release of Endothelin from the Porcine Aorta: Inhibition by Endothelium-Derived Nitric Oxide,” Journal of Clinical Investigation, Vol. 85, No. 2, 1990, pp. 587-590.
[11]	J. R. R. Fazan, V. J. D. Silva and H. C. Salgado, “Modelos de hipertens?o Arterial,” Revista Brasileira de Hipertens?o, Vol. 8, No. 1, 2001, pp. 19-29.
[12]	G. De Simone, R. B. Devereux, M. Chinali, M. J. Roman, L. G. Best, T. K. Welty, E. T. Lee and B. V. Howard, “Strong Heart Study Investigators: Risk Factors for Arterial Hypertension in Adults with Initial Optimal Blood Pressure: The Strong Heart Study,” Hypertension, Vol. 47, No. 2, 2006, pp. 162-167.
[13]	M. Usui, K. Egashira, S. Kitamoto, M. Koyanagi, M. Katoh, C. Kataoka, H. Shimokawa and A. Takeshita, “Pathogenic Role of Oxidative Stress in Vascular Angiotensin-Converting Enzyme Activation in Long-Term Blockade of Nitric Oxide Synthesis in Rats,” Hypertension, Vol. 34, No. 4, 1999, pp. 546-551
[14]	S. Moncada and A. Higgs, “The L-Arginine-Nitric Oxide Pathway,” The New England Journal of Medicine, Vol. 329, No. 27, 1993, pp. 2002-2012.
[15]	R. Busse and I. Fleming, “Endothelial Dysfunction in Atherosclerosis,” Journal of Vascular Research, Vol. 33, No. 3, 1996, pp. 181-194.
[16]	D. G. Harrison, “Endothelial Function and Oxidant Stress,” Clinical Cardiology, Vol. 20, No. 11, 1997, pp. II-11-II-17.
[17]	G. Kojdaa and D. Harrisonb, “Interactions between NO and Reactive Oxygen Species: Pathophysiological Importance in Atherosclerosis, Hypertension, Diabetes and Heart Failure,” Cardiovascular Research, Vol. 43, No. 3, 1999, pp. 562-571.
[18]	G. P. Rossi, A. Sacchetto, M. Cesari and A. C. Pessina, “Interactions between Endothelin-1 and the Renin-Angiotensin-Aldosterone System,” Cardiovascular Research, Vol. 43, No. 2, 1999, pp. 300-307.
[19]	N. Kaul, N. Siveski-Iliskovic, M. Hill, J. Slezak and K. Singal, “Free Radicals and the Heart,” Journal of Pharmacological and Toxicological Methods, Vol. 30, No. 2, 1993, pp. 55-67.
[20]	P. K. Singal, N. Khaper, A. Belló-Klein and M. Bhayana, “Oxidative Stress Status in the Transition of Hypertrophy to Heart Failure,” Heart Failure Reviews, Vol. 4, No. 4, 1999, pp. 353-360.
[21]	P. K. Singal, N. Khaper, F. Farahmand and A. BellóKlein, “Oxidative Stress in Congestive Heart Failure,” Current Cardiology Reports, Vol. 2, No. 3, 2000, pp. 206-211.
[22]	K. Kathy, K. K. Griendling, A. Garret and M. D. FitzGerald, “Oxidative Stress and Cardiovascular Injury,” Circulation, Vol. 108, 2003, pp. 1912-1916.
[23]	F. Liao, A. Andalibi, J. H. Qiao, H. Allayee, A. M. Fogelman and A. J. Lusis, “Genetic Evidence for a Common Pathway Mediating Oxidative Stress, Inflammatory Gene Induction, and Aortic Fatty Streak Formation in Mice,” The Journal of Clinical Investigation, Vol. 94, No. 2, 1994, pp. 877-884.
[24]	B. Halliwell and J. M. Gutteridge, “Antioxidant Defences: Endogenous and Diet Derived,” In: K. Davies, Ed., Free Radicals in Biology and Medicine, Elsevier Inc., New York, 2007, p.
[25]	G. J. Soleas, E. P. Diamandis and G. D. M. Goldber, “Resveratrol: A Molecule Whose Time Has Come? And Gone?” Clinical Biochemistry, Vol. 30, No. 2, 1997, pp. 91-113.
[26]	S. Renaud and M. D. Lorgeril, “Wine, Alcohol, Platelets, and the French Paradox for Coronary Heart Disease,” Lancet, Vol. 339, No. 8808, 1992, pp. 1523-1526.
[27]	L. Frémont, L. Belguendouz and S. Delpal, “Antioxidant Activity of Resveratrol and Alcohol-Free Wine Polyphenols Related to LDL Oxidation and Polyunsaturated Fatty Acids,” Life Science, Vol. 64, No. 26, 1999, pp. 25112521.
[28]	M. Murias, W. Jager, N. Handler, T. Erker, Z. Horvath, T. Szekeres, H. Nohl and L. Gille, “Antioxidant, Prooxidant and Cytotoxic Activity of Hydroxylated Resveratrol Analogues: Structure-Activity Relationship,” Biochemical Pharmacology, Vol. 69, No. 6, 2005, pp. 903-912.
[29]	T. Wallerath, D. G?ran, T. Ternes, H. Anderson, H. Li, K. Witte and U. F?rstermann, “Resveratrol, a Polyphenolic Phytoalexin Present in Red Wine, Enhances Expression and Activity of Endothelial Nitric Oxide Synthase,” Circulation, Vol. 106, No. 13, 2002, pp. 1652-1658.
[30]	M. E. Juan, M. P. Vinardell and J. M. Planas, “The Daily Oral Administration of High Doses of Trans-Resveratrol to Rats for 28 Days Is Not Harmful,” Journal of Nutrition, Vol. 132, No. 2, 2002, pp. 257-260.
[31]	R. E. Widdop and X. C. Li, “A Simple Versatile Method for Measuring Tail Cuff Systolic Blood Pressure in Conscious Rats,” Clinical Science (London, England: 1979), Vol. 93, No. 3, 1997, pp. 191-194.
[32]	A. S. Araújo, M. F. Ribeiro, A. Enzveiler, P. Schenkel, T. R. Fernandes, W. A. Partata, M. C. Irigoyen, S. Llesuy and A. Belló-Klein, “Myocardial Antioxidant Enzyme Activities and Concentration and Glutathione Metabolism in Experimental Hyperthyroidism,” Molecular and Cellular Biochemistry, Vol. 240, No. 1-2, 2006, pp. 133-139.
[33]	C. Urso and G. Caimi, “Oxidative Stress and Endothelial Dysfunction,” Minerva Medica, Vol. 102, No. 1, 2011, pp. 59-77.
[34]	R. Ross, “Atherosclerosis—An Inflamatory Disease,” The New England Journal of Medicine, Vol. 340, No. 2, 1999, pp. 115-126.
[35]	M. C. Aubin, C. Lajoie, R. Clément, H. Gosselin, A. Calderone, L. P. Perrault, “Female Rats Fed a High-Fat Diet Were Associated with Vascular Dysfunction and Cardiac Fibrosis in the Absence of Overt Obesity and Hyperlipidemia: Therapeutic Potential of Resveratrol,” Journal of Pharmacology and Experimental Therapeutics, Vol. 325, No. 3, 2008, pp. 961-968.
[36]	Z. Liu, Y. Song, X. Zhang, Z. Liu, W. Zhang, W. Mao, W. Wang, W. Cui, X. Zhang, X. Jia, N. Li, C. Han and C. Liu, “Effects of Trans-Resveratrol on HypertensionInduced Cardiac Hypertrophy Using the Partially Nephrectomized Rat Model,” Clinical and Experimental Pharmacology and Physiology, Vol. 32, No. 12, 2005, pp. 1049-1054.
[37]	R. Miatello, M. Vázquez, N. Renna, M. Cruzado, A. P. Zumino and N. Risler, “Chronic Administration of Resveratrol Prevents Biochemical Cardiovascular Changes in Fructose-Fed Rats,” American Journal of Hypertension, Vol. 18, No. 6, 2005, pp. 864-870.
[38]	J. Behbahani, S. J. Thandapilly, K. L. Louis, Y. Huang, Z. Shao, M. A. Kopilas, P. Wojciechowski, T. Netticadan, H. D. Anderson, “Resveratrol and Small Artery Compliance and Remodeling in the Spontaneously Hypertensive Rat,” American Journal of Hypertension, Vol. 23, No. 12, 2010, pp. 1273-1278.
[39]	H. Z. Toklu, O. Sehirli, M. Er?ahin, S. Süleym0ano?lu, O. Yi?iner, E. Emekli-Alturfan, A. Yarat, B. ?. Ye?en and G. Sener, “Resveratrol Improves Cardiovascular Function and Reduces Oxidative Organ Damage in the Renal, Cardiovascular and Cerebral Tissues of Two-Kidney, OneClip Hypertensive Rats,” Journal of Pharmacy and Pharmacology, Vol. 62, No. 12, 2010, pp. 1784-1793.
[40]	U. G. B. Haider, D. Sorescu, K. K. Griendling, A. M. Vollmar and V. M. Dirsch, “Resveratrol Suppresses Angiotensin II-Induced Akt/Protein Kinase B and P70 S6 Kinase Phosphorylation and Subsequent Hypertrophy in Rat Aortic Smooth Muscle Cells,” Molecular Pharmacology, Vol. 62, No. 4, 2002, pp. 772-777.
[41]	T. H. Cheng, J. C. Liu, H. Lin, N. L. Shih, Y. L. Chen, M. T. Huang, P. Chan, C. F. Cheng and J. F. Chen, “Inhibitory Effect of Resveratrol on Angiotensin II-Induced Cardiomyocyte Hypertrophy,” Naunyn-Schmiedeberg’s Archives of Pharmacology, Vol. 369, No. 2, 2004, pp. 239-244.
[42]	E. Takimoto and D. A. Kass, “Role of Oxidative Stress in Cardiac Hypertrophy and Remodeling,” Hypertension, Vol. 49, No. 2, 2007, pp. 241-248.
[43]	G. E. Callera, A. Yogi, R.C. Tostes, L. V. Rossoni and L. M. Bendhack, “Ca2+ Activated K+ Channels Underlying the Impaired Acetylcholine-Induced Vasodilation in 2k1c Hypertensive Rats,” The Journal of Pharmacology and Experimental Therapeutic, Vol. 309, No. 3, 2004, pp. 1036-1042.
[44]	J. K. Amin, L. Xiao, D. R. Pimental, P. J. Pagano, K. Singh, D. B. Sawyer and W. S. Colucci, “Reactive Oxygen Species Mediate Alpha-Adrenergic Receptor-Stimulated Hypertrophy in Adult Rat Ventricular Myocytes,” Journal of Molecular and Cellular Cardiology, Vol. 33, No. 1, 2011, pp. 131-139.
[45]	H. Cai, K. K. Griendling and D. G. Harrison, “The Vascular NAD(P)H Oxidases as Therapeutic Targets in Cardiovascular Diseases,” Trends in Pharmacological Sciences, Vol. 24, No. 9, 2003, pp. 471-478.
[46]	P. T. Nowicki, S. Flavahan, H. Hassanain, S. Mitra, S. Holland, P. J. Goldschmidt-Clermont and N. A. Flavahan, “Redox Signaling of the Arteriolar Myogenic Response,” Circulation Research, Vol. 89, No. 2, 2001, pp. 114-116.
[47]	M. H. Tsai and M. J. Jiang, “Reactive Oxygen Species Are Involved in Regulating Alpha1-Adrenoceptor-Activated Vascular Smooth Muscle Contraction,” Journal of Biomedical Science, Vol. 23, No. 17, 2010, pp. 67.
[48]	J. A. Baur and D. A. Sinclair, “Therapeutic Potential of Resveratrol: The in Vivo Evidence,” Nature Reviews Drug Discovery, Vol. 5, No. 6, 2006, pp. 493-506.
[49]	K. Mizutani, K. Ikeda, Y. Kawai and Y. Yamori, “Resveratrol Attenuates Ovariectomy-Induced Hypertension and Bone Loss in Stroke-Prone Spontaneously Hypertensive Rats,” Journal of Nutritional Science and Vitaminology, Vol. 46, No. 2, 2000, 78-83.
[50]	C. Silan, “The Effects of Chronic Resveratrol Treatment on Vascular Responsiveness of Streptozotocin-Induced Diabetic Rats,” Biological & Pharmaceutical Bulletin, Vol. 31, No. 5, 2008, pp, 897-902.
[51]	H. Zhang, J. Zhang, Z. Ungvari and C. Zhang, “Resveratrol Improves Endothelial Function: Role of TNF{Alpha} and Vascular Oxidative Stress,” Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 29, No. 8, 2009, pp. 1164-1171.
[52]	J. G. Zou, Z. R. Wang, Y. Z. Huang, K. J. Cao and L. M. Wu, “Effect of Red Wine And Wine Polyphenol Resveratrol on Endothelial Function in Hypercholesterolemic Rabbits,” International Journal of Molecular Medicine, Vol. 11, No. 3, 2003, pp. 317-320.
[53]	R. H. Wong, P. R. Howe, J. D. Buckley, A. M. Coates, I. Kunz and N. M. Berry, “Acute Resveratrol Supplementation Improves Flow-Mediated Dilatation in Overweight/Obese Individuals with Mildly Elevated Blood Pressure,” Nutrition, Metabolism & Cardiovascular Diseases, Vol. 21, No. 11, 2011, pp. 851-856.
[54]	P. Basu, N. Qipshidze, S. C. Tyagi and U. Sen, “Remodeling in Vein Expresses Arterial Phenotype in Hyperhomocysteinemia,” International Journal of Physiology, Pathophysiology and Pharmacology, Vol. 3, No. 4, 2011, pp. 266-279.
[55]	U. Landmesser, S. Dikalov, S. R. Pric, L. MCcann, T. Fukai, S. M. Holland, W. E. Mitch and D. G. Harrison, “Oxidation of Tetrahydrobiopterin Leads to Uncoupling of Endothelial Cell Nitric Oxide Synthase In Hypertension,” The Journal of Clinical Investigation, Vol. 111, No. 8, 2003, pp. 1201-1209.
[56]	R. M. Touyz, “Reactive Oxygen Species in Vascular Biology: Role in Arterial Hypertension,” Expert Review of Cardiovascular Therapy, Vol. 1, No. 1, 2003, pp. 91106.
[57]	B. Lasségue and K. K. Griendling, “Reactive Oxygen Species in Hypertension,” American Journal of Hypertension, Vol. 17, No. 9, 2004, pp. 852-860.
[58]	H. Li and N. Xia, “F?rstermann. Cardiovascular Effects and Molecular Targets of Resveratrol,” Nitric Oxide, Vol. 26, No. 2, 2012, pp. 102-110.
[59]	U. F?rstermann and H. Li, “Therapeutic Effect of Enhancing Endothelial Nitric Oxide Synthase (eNOS) Expression and Preventing eNOS Uncoupling,” British Journal of Pharmacology, Vol. 164, No. 2, 2011, pp. 213-223.
[60]	S. Soylemez, A. Sepici and F. Akar, “Resveratrol Supplementation Gender Independently Improves Endothelial Reactivity and Suppresses Superoxide Production in Healthy Rats,” Cardiovascular Drugs and Therapy, Vol. 23, No, 6, 2009, pp. 449-458.
[61]	C. M. Klinge, N. S. Wickramasinghe, M. M. Ivanova and S. M. Dougherty, “Resveratrol stimulates Nitric Oxide Production by Increasing Estrogen Receptor Alpha-SrcCaveolin-1 Interaction And Phosphorylation In Human Umbilical Vein Endothelial Cells,” The FASEB Journal, Vol. 22, No. 7, 2008, pp. 2185-2197.
[62]	V. W. Dolinsky, A. Y. Chan, I. Robillard Frayne, P. E. Light, C. Des Rosiers and J. R. Dyck, “Resveratrol Prevents the Prohypertrophic Effects of Oxidative Stress on LKB1,” Circulation, Vol. 119, No. 12, 2009 pp. 16431652.
[63]	S. J. Thandapilly, P. Wojciechowski, J. Behbahani, X. L. Louis, L. Yu, D. Juric, M. A. Kopilas, H. D. Anderson and T. Netticadan, “Resveratrol Prevents the Development of Pathological Cardiac Hypertrophy and Contractile Dysfunction in the SHR without Lowering Blood Pressure,” American Journal of Hypertension, Vol. 23, No. 2, 2010, pp. 192-196.
[64]	A. Y. Chan, V. W. Dolinsky, C. L. Soltys, B. Viollet, S. Baksh, P. E. Light and J. R. Dyck, “Resveratrol Inhibits Cardiac Hypertrophy via AMP-Activated Protein Kinase and Akt,” The Journal of Biological Chemistry, Vol. 283, No. 35, 2008, pp. 24194-24201.