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http://dx.doi.org/10.5352/JLS.2011.21.10.1415

Effects of L-Arginine Supplementation and Regular Exercise in D-Galactose Induced Aging Rat Aorta: Study on Inflammatory Factors, Vasodilation Regulatory Factors  

Lee, Jin (Department of Anatomy and Cell Biology, Collage of Medicine, Han-Yang University)
Kwak, Yi-Sub (Department of Physical Education, Dong Eui University)
Yoo, Young-June (Department of Physical Education, Sejong University)
Park, Sok (Department of Physiology, Collage of Medicine, Aju University)
Publication Information
Journal of Life Science / v.21, no.10, 2011 , pp. 1415-1421 More about this Journal
Abstract
The purpose of this study was to identify the effects of an L-arginine supplementation and regular exercise training on NF-${\kappa}B$, TNF-${\alpha}$, iNOS, Cav-1, eNOS and Ang II in the aortas of D-galactose (D-gal) induced aging rats. The male Strague-Dawley rats were treated with a D-galactose aging inducing agent; the D-gal injection (50 mg/kg) was given intraperitoneally for 12 wk. Experimental groups were divided into five groups: (1) Young control group (Y-Con, n=8), (2) Aging control group (A-Con, n=8), (3) Aging exercise group (A-Ex, n=8), (4) Aging exercise group with L-arginine supplementation group (A-Ex+A, n=8), and (5) Aging with L-arginine supplementation group (A-A, n=8). The exercise consisted of running on a treadmill for 60 min/day at 20 m/min for 6 day/wk, at 0% gradient for 12 wk. The L-arginine supplementation was given orally at a dose of 150 mg/kg/day for 12 wk. The findings of this study were as follows: 1. NF-${\kappa}B$, TNF-${\alpha}$, iNOS, Cav-1 and Ang II proteins in the aortas of D-gal induced rats were significantly increased, however, L-arginine supplementation and regular exercise resulted in a significant inhibition in the expression of NF-${\kappa}B$, TNF-${\alpha}$, iNOS, Cav-1 and Ang II proteins. 2. eNOS protein in the aortas of D-gal induced rats was significantly decreased, however, L-arginine supplementation and regular exercise resulted in a significant increase in the expression of eNOS proteins. In conclusion, the findings of the present study reveal that L-arginine supplementation alone or regular exercise alone or in combination with L-arginine supplementation for 12 wk increases anti-inflammatory effects by decreasing NF-${\kappa}B$, TNF-${\alpha}$, and iNOS protein expressions within the aortic tissue. In addition, L-arginine supplementation alone or regular exercise alone or in combination with L-arginine supplementation may prevent endothelial function by up-regulation of eNOS protein in the aortas of D-gal induced aging rats.
Keywords
Aging rats; regular exercise; NF-${\kappa}B$; TNF-${\alpha}$; iNOS; Ang II; Cav-1; eNOS; aorta;
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1 Wolf, G. 2002. Free radical production and angiotensin. Curr. Hypertens. Rep. 2, 167-173.
2 Yamada, E. 1955. The fine structure of gall bladder epithelium of the mouse. J. Bio-phys. Biochem. Cytol. 1, 445-458.   DOI
3 Linda, S. P., A. F. Barry, F. Robert, B. F. William, A. K. George, and A. R. Chester. 2004. Exercise and hypertension. Med. Sci. Sports Exercise 3603, 533-553.
4 Lei, M., X. Hua, M. Xiao, J. Ding, Q. Han, and G. Hu. 2008. Impairments of astrocytes are involved in the D-galactose-induced brain aging. Biochem. Biophys. Res. Commun. 369, 1082-1087.   DOI
5 Long, J., X. Wang, H. Gao, Z. Liu, C. Liu, M. Miao, X. Cui, L. Packer, and J. Liu. 2007. D-Galactose toxicity in mice is associated with mitochindrial dysfunction: protection effects of mitochondrial nutrient R-alpha-lipoic acid. Biogerontology 8, 373-381.   DOI
6 Makarov, S. 2000. NF-kappa B as a therapeutic target in chronic inflammation: recent advances. Mol. Med. Today 6, 441-448.   DOI
7 Moncada, S., R. M. Palmer, and E. A. Higgs. 1991. Nitric oxide: physiology and pharmacology. Pharmacol. Rev. 43, 109-142.
8 Orozco-Gutiѐrrez, J. J., L. Castillo-Martinez, A. Orea- Tejeda, O. Vazquez-Diaz, A. Valdespino-Trejo, R. Narvaez-David, C. Keirns-Davis, O. Carrasco-Ortiz, A. Navarro-Navarro, and R. Sanchez-Santillan. 2010. Effect of L-arginine or L-citrulline oral supplementation on blood pressure and right ventricular function in heart failure patients with preserved ejection fraction. Cardiol. J. 17, 612-618
9 Sessa, W. C., K. Pritchard, and N. I. Seyei. 1994. Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ. Res. 74, 349-353.   DOI   ScienceOn
10 Seo, A. Y., T. Hofer, B. Sung, S. Judge, H. Y. Chung, and C. Leeuwenburgh. 2006. Hepatic oxidative stress during aging: effects of 8% long-term calorie restriction and lifelong exercise. Antioxid. Redox. Signal. 8, 529-538.   DOI
11 Song, X., M. Bao, D. Li, and Y. M. Li. 1999. Advanced glycation in D-galactose induced mouse aging model. Mech. Aging. Dev. 108, 239-251.   DOI
12 Graham, D. A. and J. W. Rush. 2004. Exercise training improves aortic endothelium-dependent vasorelaxation and determinants of nitric oxide bioavailability in spontaneously hypertension rats. J. Appl. Physiol. 96, 2088-2096.   DOI
13 Feron, O., L. Belhassen, L. Kobzik, T. W. Smith, R. A. Kelly, and T. Michel. 1996. Endothelial nitric oxide synthase targeting to caveolae. Specific interactions with caveolin isoforms in cardiac myocytes and endothelial cells. J. Biol. Chem. 271, 22810-22814.   DOI
14 Garcia-Cardena, G., P. Martasek, B. S. Siler-Masters, P. M. Skidd, J. C. Couet, S. Li, M. P. Lisanti, and W. C. Sessa. 1998. Dissecting the interaction between nitric oxide synthase (NOS) and caveolin: Functional significance of the NOS caveolin binding domain in vivo. J. Biol. Chem. 272, 25437-25440.
15 Gerhard, M., M. A. Roddy, S. J. Creager, and M. A. Creager. 1996. Aging progressively impairs endothelium dependent vasorelaxation in forearm resistance vessles of humans. Hypertension 27, 849-853.   DOI
16 Green, D. J., G. O'Driscoll, B. A. Blanksby, and R. R. Taylor. 1996. Control skeletal muscle blood during dynamic exercise. Sports Med. 21, 119-146.   DOI
17 Hambrecht, R., L. Hilbrich, S. Erbs, S. Gielen, E. Fiehn, N. Schuler, and G. Schuler. 2000. Correction of endothelial dysfunction in chronic heart failure: additional effects of exercise training and oral L-arginine supplementation. J. Am. Coll. Cardiol. 35, 706-713.   DOI
18 Ishihata, A. and Y. Katano. 2006. Role of angiotensin II and endothelin-1 receptors in aging-related functional changes in rat cardiovascular system. Ann. N. Y. Acad. Sci. 1067, 173-181.   DOI
19 Jankord, R. and B. Jemiolo. 2004. Influence of physical activity on serum IL-6 and IL-10 levels in healthy older men. Med. Sci. Sports Exerc. 36, 960-964.   DOI
20 Chung, H. Y., H. J. Kim, K. W. Kim, J. S. Choi, and B. P. Yu. 2002. Molecular inflammation hypothesis of aging based on the anti-aging mechanism of calorie restriction. Microsc. Res. Tech. 59, 264-272.   DOI
21 Chang, S. P., Y. H. Chen, W. C. Chang, I. M. Liu, and J. T. Cheng. 2004. Increase of anti-oxidation by exercise in the liver of obese Zucker rats. Clin. Exp. Pharmacol. Physiol. 31, 506-511.   DOI
22 Chung, H. Y., B. Sung, K. J. Jung, Y. Zou, and B. P. Yu. 2006. The molecular inflammatory process in aging. Antioxid. Redox. Signal. 8, 572-581.   DOI
23 Chung, H. Y., M. Cesari, S. Anton, E. Maezetti, S. Giovannini, A. Y. Seo, C. Carter, B. P. Tu, and C. Leeuwenburgh. 2009. Molecular inflammation: underpinnings of aging and age-related diseases. Aging. Res. Rev. 8, 18-30.   DOI
24 Colbert, L. H., M. Visser, E. M. Simonsick, R. P. Tracy, A. B. Newman, S. B. Kritchevsky, M. Pahor, D. R. Taaffe, J. Brach, S. Rubin, and T. B. Harris. 2004. Physical activity, exercise, and inflammatory markers in older adults: findings from the health, aging and body composition study. J. Am. Geriatr. Soc. 52, 1098-1104.   DOI
25 de Somomayor, M. A., C. Perez-Guerrero, M. D. Herrrera, L. Jimenez, R. Marin, E. Marhuenda, and R. Andriantsitohaina. 2005. Improvement of age-related endothelial dysfunction by simvastatin: effect on NO and COX pathways. Br. J. Pharmacol. 146, 1130-1138.
26 Ding, G., K. Reddy, A. A. Kapasi, N. Franki, N. Gibbons, B. S. Kasinath, and P. C. Singhal. 2002. Angiotensin II induces apoptosis in rat glomerular epithelial cells. Am. J. Physiol. Renal. Physiol. 283, 173-180.
27 Dohi, Y., M. Kojima, K. Sato, and T. F. Luscher. 1995. Age-related changes in vascular smooth muscle and endothelium. Drugs Aging 7, 278-291.   DOI
28 Braunwald, E. 1997. Shattuck lecture-Cardiovascular medicine at the turn of the millenium: triumphs, concerns, and opportunities. N. Engl. J. Med. 337, 1360-1369.   DOI
29 Adriao, M., C. J. Chrisman, M. Bielavsky, S. C. Olinto, E. M. Shiraishi, and M. T. Nunes. 2004. Arginine increases growth hormone gene expression in rat pituitary and GH3 cells. Neuroendocrinology 79, 26-33.   DOI
30 Boger, R. H. and S. M. Bode-Boger. 2001. The clinical pharmacology of L-arginine. Annu. Rev. Pharmacol. Toxicol. 41, 79-99.   DOI
31 Brod, S. A. 2000. Unreulated inflammation shortens human functional longevity. Inflamm Res. 49, 561-570.   DOI
32 Bradford, M. M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248-254.   DOI   ScienceOn
33 Carman, C. V., M. P. Lisanti, and J. L. Benovic. 1999. Regulation of G protein-coupled receptor kinases by caveolin. J. Biol. Chem. 274, 8858-8864.   DOI
34 Cho, K. A., S. J. Ryu, J. S. Park, I. S., Jang, J. S. Ahn, K. T. Kim, and S. C. Park. 2003. Senescent phenotype can be reversed by reduction of caveolin status. J. Biol. Chem. 278, 27789-27795.   DOI