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Background and Objectives: L-arginine is the substrate for vascular nitric oxide (NO) formation. It has antihypertensive, antioxidant, and anti-inflammatory activities. This study was to investigate the effect of L-arginine on blood pressure and vascular endothelial function in Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats.
Methods: Male Sprague-Dawley rats were administered with L-NAME (40 mg/kg/day) in drinking water for 5 weeks in order to induce hypertension. Hypertensive rats were treated with L-arginine (100 mg/kg/day) or vehicle for the last 2 weeks. Systolic blood pressure was measured weekly. Vascular endothelial function test, plasma NO metabolite (NOx), and vascular superoxide (O2•−) production were evaluated.
Results: Rats treated with L-NAME had high blood pressure and endothelial dysfunction associated with decreased plasma NOx level and increased vascular O2•− production comparing to control (p<0.05). L-arginine significantly reduced blood pressure, and improved vascular endothelial function in L-NAME-treated rats (p<0.05). Moreover, L-arginine enhanced nitric oxide bioavailability by restoring plasma NOx level and reducing O2•− production in hypertensive rats (p<0.05).
Conclusion: Our results indicated that L-arginine decreased blood pressure and alleviated vascular endothelial dysfunction in L-NAME-induced hypertensive rats. This was associated with increasing in NO bioavailability.
2. Ribeiro MO, Antunes E, de Nucci G, Lovisolo SM, Zatz R. Chronic inhibition of nitric oxide synthesis. A new model of arterial hypertension. Hypertension 1992; 20: 298-303.
3. Moore PK, Oluyomi AO, Babbedge RC, Wallace P, Hart SL. L-NG-nitro arginine methyl ester exhibits antinociceptive activity in the mouse. Br J Pharmacol 1991; 102: 198-202.
4. Bunbupha S, Pakdeechote P, Kukongviriyapan U, Prachaney P, Kukongviriyapan V. Asiatic acid reduces blood pressure by enhancing nitric oxide bioavailability with modulation of eNOS and p47phox expression in L-NAME-induced hypertensive rats. Phytother Res 2014; 28: 1506-12.
5. Fu JY, Qian LB, Zhu LG, Liang HT, Tan YN, Lu HT, et al. Betulinic acid ameliorates endothelium-dependent relaxation in L-NAME-induced hypertensive rats by reducing oxidative stress. Eur J Pharm Sci 2011; 44: 385-91.
6. Luiking YC, Ten Have GA, Wolfe RR, Deutz NE. Arginine de novo and nitric oxide production in disease states. Am J Physiol Endocrinol Metab 2012; 303: E1177-89.
7. Suliburska J, Bogdanski P, Krejpcio Z, Pupek-Musialik D, Jablecka A. The effects of L-arginine, alone and combined with vitamin C, on mineral status in relation to its antidiabetic, anti-inflammatory, and antioxidant properties in male rats on a high-fat diet. Biol Trace Elem Res 2014; 157: 67-74.
8. Ahmad A, Sattar MZ, Rathore HA, Hussain AI, Khan SA, Fatima T, et al. Antioxidant Activity and Free Radical Scavenging Capacity of L-Arginine and Nahs: A Comparative in Vitro Study. Acta Pol Pharm 2015; 72: 245-52.
9. Hnia K, Gayraud J, Hugon G, Ramonatxo M, De La Porte S, Matecki S, et al. L-arginine decreases inflammation and modulates the nuclear factor-kappaB/matrix metalloproteinase cascade in mdx muscle fibers. Am J Pathol 2008; 172: 1509-19.
10. Tay A, Ozcelikay AT, Altan VM. Effects of L-arginine on blood pressure and metabolic changes in fructose-hypertensive rats. Am J Hypertens 2002; 15: 72-7.
11. Sumou IK, Du JB, Wei B, Zhang CY, Qi JG, Tang CS. Effect of L-arginine on pulmonary artery smooth muscle cell apoptosis in rats with hypoxic pulmonary vascular structural remodeling. Acta Biochim Biophys Sin (Shanghai) 2006; 38: 15-21.
12. Goret L, Tanguy S, Guiraud I, Dauzat M, Obert P. Acute administration of l-arginine restores nitric oxide-mediated relaxation in isolated pulmonary arteries from pulmonary hypertensive exercise trained rats. Eur J Pharmacol 2008; 581: 148-56.
13. Ramos L, Labat R, Carvalho FA, Martin AB, Lopes-Martins RA. Effect of oral arginine administration over blood pressure and cardiac parameters in rats submitted to chronic inhibition of nitric oxide synthesis. Rev Bras Med Esporte 2006; 12: 152e-6e.
14. Lu FJ, Lin JT, Wang HP, Huang WC. A simple, sensitive, non-stimulated photon counting system for detection of superoxide anion in whole blood. Experientia 1996; 52: 141-4.
15. Luangaram S, Kukongviriyapan U, Pakdeechote P, Kukongviriyapan V, Pannangpetch P. Protective effects of quercetin against phenylhydrazine-induced vascular dysfunction and oxidative stress in rats. Food Chem Toxicol 2007; 45: 448-55.
16. Verdon CP, Burton BA, Prior RL. Sample pretreatment with nitrate reductase and glucose-6-phosphate dehydrogenase quantitatively reduces nitrate while avoiding interference by NADP+ when the Griess reaction is used to assay for nitrite. Anal Biochem 1995; 224: 502-8.
17. Nakmareong S, Kukongviriyapan U, Pakdeechote P, Donpunha W, Kukongviriyapan V, Kongyingyoes B, et al. Antioxidant and vascular protective effects of curcumin and tetrahydrocurcumin in rats with L-NAME-induced hypertension. Naunyn Schmiedebergs Arch Pharmacol 2011; 383: 519-29.
18. Lerman A, Burnett JC, Jr., Higano ST, McKinley LJ, Holmes DR, Jr. Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation 1998; 97: 2123-8.
19. Pryor WA, Squadrito GL. The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am J Physiol 1995; 268: L699-722.
20. Kohli R, Meininger CJ, Haynes TE, Yan W, Self JT, Wu G. Dietary L-arginine supplementation enhances endothelial nitric oxide synthesis in streptozotocin-induced diabetic rats. J Nutr 2004; 134: 600-8.
21. Kawano H, Motoyama T, Hirai N, Kugiyama K, Yasue H, Ogawa H. Endothelial dysfunction in hypercholesterolemia is improved by L-arginine administration: possible role of oxidative stress. Atherosclerosis 2002; 161: 375-80.