Korean J Physiol Pharmacol.  2013 Aug;17(4):339-345. 10.4196/kjpp.2013.17.4.339.

Effect of Lutein on L-NAME-Induced Hypertensive Rats

Affiliations
  • 1College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea. simss@cau.ac.kr

Abstract

We investigated the antihypertensive effect of lutein on NG-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. Daily oral administration of L-NAME (40 mg/kg)-induced a rapid progressive increase in mean arterial pressure (MAP). L-NAME significantly increased MAP from the first week compared to that in the control and reached 193.3+/-9.6 mmHg at the end of treatment. MAP in the lutein groups was dose-dependently lower than that in the L-NAME group. Similar results were observed for systolic and diastolic blood pressure of L-NAME-induced hypertensive rats. The control group showed little change in heart rate for 3 weeks, whereas L-NAME significantly reduced heart rate from 434+/-26 to 376+/-33 beats/min. Lutein (2 mg/kg) significantly prevented the reduced heart rate induced by L-NAME. L-NAME caused hypertrophy of heart and kidney, and increased plasma lipid peroxidation four-fold but significantly reduced plasma nitrite and glutathione concentrations, which were significantly prevented by lutein in a dose-dependent manner. These findings suggest that lutein affords significant antihypertensive and antioxidant effects against L-NAME-induced hypertension in rats.

Keyword

Antioxidant; Hypertension; Lipid peroxidation; L-NAME; Lutein

MeSH Terms

Administration, Oral
Animals
Antioxidants
Arterial Pressure
Blood Pressure
Glutathione
Heart
Heart Rate
Hypertension
Hypertrophy
Kidney
Lipid Peroxidation
Lutein
NG-Nitroarginine Methyl Ester
Plasma
Rats
Antioxidants
Glutathione
Lutein
NG-Nitroarginine Methyl Ester

Figure

  • Fig. 1 Effect of lutein on the body weight in NG-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. (A) Weight (%), weight/initial weight. (B) Δ Weight (g), body weight on third week minus body weight on initial week. L-NAME rats fed 40 mg/kg L-NAME. L-NAME+CoQ10 rats fed L-NAME with 10 mg/kg coenzyme Q10. L-NAME+Lutein-0.5 rats fed L-NAME with 0.5 mg/kg lutein. L-NAME+Lutein-2 rats fed L-NAME with 2 mg/kg lutein. Results are expressed as mean±standard deviation of seven animals. *p<0.05 vs. normal control group, #p<0.05 vs. L-NAME control group.

  • Fig. 2 Effect of lutein on mean arterial pressure (MAP) in NG-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. (A) Time-course effect of lutein on MAP over 3 weeks. (B) Change in MAP from initial to final week. L-NAME rats fed 40 mg/kg L-NAME. L-NAME+CoQ10 rats fed L-NAME with 10 mg/kg coenzyme Q10. L-NAME+Lutein-0.5 rats fed L-NAME with 0.5 mg/kg lutein. L-NAME+Lutein-2 rats fed L-NAME with 2 mg/kg lutein. Results are expressed as mean±standard deviation of seven animals. *p<0.05 vs. normal control group, #p<0.05 vs. L-NAME control group.

  • Fig. 3 Effect of lutein on systolic blood pressure (SBP) in NG-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. (A) Time-course effect of lutein on SBP for 3 weeks. (B) Change in SBP from initial week to final week. L-NAME rats fed 40 mg/kg L-NAME. L-NAME+CoQ10 rats fed L-NAME with 10 mg/kg coenzyme Q10. L-NAME+Lutein-0.5 rats fed L-NAME with 0.5 mg/kg lutein. L-NAME+Lutein-2 rats fed L-NAME with 2 mg/kg lutein. Results are expressed as mean±standard deviation of seven animals. *p<0.05 vs. normal control group, #p<0.05 vs. L-NAME control group.

  • Fig. 4 Effect of lutein on diastolic blood pressure (DBP) in NG-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. (A) Time-course effect of lutein on DBP for 3 weeks. (B) Change in DBP from initial week to final week. L-NAME rats fed 40 mg/kg L-NAME. L-NAME+CoQ10 rats fed L-NAME with 10 mg/kg coenzyme Q10. L-NAME+Lutein-0.5 rats fed L-NAME with 0.5 mg/kg lutein. L-NAME+Lutein-2 rats fed L-NAME with 2 mg/kg lutein. Results are expressed as mean±standard deviation of seven animals. *p<0.05 vs. normal control group, #p<0.05 vs. L-NAME control group.

  • Fig. 5 Effect of lutein on heart rate in NG-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. L-NAME rats fed 40 mg/kg L-NAME. L-NAME+CoQ10 rats fed L-NAME with 10 mg/kg coenzyme Q10. L-NAME+Lutein-0.5 rats fed L-NAME with 0.5 mg/kg lutein. L-NAME+Lutein-2 rats fed L-NAME with 2 mg/kg lutein. Results are expressed as mean±standard deviation of seven animals. *p<0.05 vs. 0 week in the same group, #p<0.05 vs. L-NAME group at 3rd week.

  • Fig. 6 Effect of lutein on the cardiac (A) and renal (B) hypertrophy in NG-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. L-NAME rats fed 40 mg/kg L-NAME. L-NAME+CoQ10 rats fed L-NAME with 10 mg/kg coenzyme Q10. L-NAME+Lutein-0.5 rats fed L-NAME with 0.5 mg/kg lutein. L-NAME+Lutein-2 rats fed L-NAME with 2 mg/kg lutein. Results are expressed as mean±standard deviation of seven animals. *p<0.05 vs. normal control group, #p<0.05 vs. L-NAME control group.

  • Fig. 7 Effects of lutein on plasma nitrite concentration in NG-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. L-NAME rats fed 40 mg/kg L-NAME. L-NAME+CoQ10 rats fed L-NAME with 10 mg/kg coenzyme Q10. L-NAME+Lutein-0.5 rats fed L-NAME with 0.5 mg/kg lutein. L-NAME+Lutein-2 rats fed L-NAME with 2 mg/kg lutein. Results are expressed as mean±standard deviation of seven animals. *p<0.05 vs. normal control group, #p<0.05 vs. L-NAME control group.

  • Fig. 8 Effect of lutein on the plasma malondialdehyde (MDA) concentration in NG-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. L-NAME rats fed 40 mg/kg L-NAME. L-NAME+CoQ10 rats fed L-NAME with 10 mg/kg coenzyme Q10. L-NAME+Lutein-0.5 rats fed L-NAME with 0.5 mg/kg lutein. L-NAME+Lutein-2 rats fed L-NAME with 2 mg/kg lutein. Results are expressed as mean±standard deviation of seven animals. *p<0.05 vs. normal control group, #p<0.05 vs. L-NAME control group.

  • Fig. 9 Effect of lutein on the plasma glutathione (GSH) concentration in NG-nitro-L-arginine methyl ester hydrochloride (L-NAME)-induced hypertensive rats. L-NAME rats fed 40 mg/kg L-NAME. L-NAME+CoQ10 rats fed L-NAME with 10 mg/kg coenzyme Q10. L-NAME+Lutein-0.5 rats fed L-NAME with 0.5 mg/kg lutein. L-NAME+Lutein-2 rats fed L-NAME with 2 mg/kg lutein. Results are expressed as mean±standard deviation of seven animals. *p<0.05 vs. normal control group, #p<0.05 vs. L-NAME control group.


Reference

1. Félétou M, Vanhoutte PM. Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture). Am J Physiol Heart Circ Physiol. 2006; 291:H985–H1002. PMID: 16632549.
Article
2. Taddei S, Virdis A, Mattei P, Ghiadoni L, Sudano I, Salvetti A. Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients. Circulation. 1996; 94:1298–1303. PMID: 8822983.
3. Shin W, Cuong TD, Lee JH, Min B, Jeon BH, Lim HK, Ryoo S. Arginase inhibition by ethylacetate extract of Caesalpinia sappan lignum contributes to activation of endothelial nitric oxide synthase. Korean J Physiol Pharmacol. 2011; 15:123–128. PMID: 21860589.
4. Jacques-Silva MC, Nogueira CW, Broch LC, Flores EM, Rocha JB. Diphenyl diselenide and ascorbic acid changes deposition of selenium and ascorbic acid in liver and brain of mice. Pharmacol Toxicol. 2001; 88:119–125. PMID: 11245406.
Article
5. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991; 43:109–142. PMID: 1852778.
6. Radomski MW, Palmer RM, Moncada S. Characterization of the L-arginine:nitric oxide pathway in human platelets. Br J Pharmacol. 1990; 101:325–328. PMID: 1701676.
7. Cho EJ, Park MS, Kim SS, Kang G, Choi S, Lee YR, Chang SJ, Lee KH, Lee SD, Park JB, Jeon BH. Vasorelaxing activity of ulmus davidiana ethanol extracts in rats: activation of endothelial nitric oxide synthase. Korean J Physiol Pharmacol. 2011; 15:339–344. PMID: 22359471.
8. Bernátová I, Pechánová O, Kristek F. Mechanism of structural remodelling of the rat aorta during long-term NG-nitro-L-arginine methyl ester treatment. Jpn J Pharmacol. 1999; 81:99–106. PMID: 10580377.
9. Fink J, Fan NY, Rosenfeld L, Stier CT Jr. Contribution of endothelin to the acute pressor response of L-NAME in stroke-prone spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1998; 31:618–622. PMID: 9554813.
Article
10. Nakanishi K, Mattson DL, Cowley AW Jr. Role of renal medullary blood flow in the development of L-NAME hypertension in rats. Am J Physiol. 1995; 268:R317–R323. PMID: 7864223.
Article
11. 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. PMID: 1516948.
Article
12. Rees DD, Palmer RM, Moncada S. Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci U S A. 1989; 86:3375–3378. PMID: 2497467.
Article
13. Sommerburg O, Keunen JE, Bird AC, van Kuijk FJ. Fruits and vegetables that are sources for lutein and zeaxanthin: the macular pigment in human eyes. Br J Ophthalmol. 1998; 82:907–910. PMID: 9828775.
Article
14. Curran-Celentano J, Hammond BR Jr, Ciulla TA, Cooper DA, Pratt LM, Danis RB. Relation between dietary intake, serum concentrations, and retinal concentrations of lutein and zeaxanthin in adults in a Midwest population. Am J Clin Nutr. 2001; 74:796–802. PMID: 11722962.
Article
15. Dwyer JH, Navab M, Dwyer KM, Hassan K, Sun P, Shircore A, Hama-Levy S, Hough G, Wang X, Drake T, Merz CN, Fogelman AM. Oxygenated carotenoid lutein and progression of early atherosclerosis: the Los Angeles atherosclerosis study. Circulation. 2001; 103:2922–2927. PMID: 11413081.
16. Parker RS. Absorption, metabolism, and transport of carotenoids. FASEB J. 1996; 10:542–551. PMID: 8621054.
Article
17. Bhattacharyya S, Datta S, Mallick B, Dhar P, Ghosh S. Lutein content and in vitro antioxidant activity of different cultivars of Indian marigold flower (Tagetes patula L.) extracts. J Agric Food Chem. 2010; 58:8259–8264. PMID: 20568770.
18. Kim JH, Na HJ, Kim CK, Kim JY, Ha KS, Lee H, Chung HT, Kwon HJ, Kwon YG, Kim YM. The non-provitamin A carotenoid, lutein, inhibits NF-kappaB-dependent gene expression through redox-based regulation of the phosphatidylinositol 3-kinase/PTEN/Akt and NF-kappaB-inducing kinase pathways: role of H(2)O(2) in NF-kappaB activation. Free Radic Biol Med. 2008; 45:885–896. PMID: 18620044.
19. Kritchevsky SB, Bush AJ, Pahor M, Gross MD. Serum carotenoids and markers of inflammation in nonsmokers. Am J Epidemiol. 2000; 152:1065–1071. PMID: 11117616.
Article
20. Rowley K, Walker KZ, Cohen J, Jenkins AJ, O'Neal D, Su Q, Best JD, O'Dea K. Inflammation and vascular endothelial activation in an Aboriginal population: relationships to coronary disease risk factors and nutritional markers. Med J Aust. 2003; 178:495–500. PMID: 12741936.
Article
21. Rao AV. Lycopene, tomatoes, and the prevention of coronary heart disease. Exp Biol Med (Maywood). 2002; 227:908–913. PMID: 12424333.
Article
22. Weisburger JH. Lycopene and tomato products in health promotion. Exp Biol Med (Maywood). 2002; 227:924–927. PMID: 12424336.
Article
23. Lee DH, Park JE, Kang YJ, Lee KY, Choi HC. Nitric oxide donor, NOR-3, increased expression of Cyclooxygenase-2, but not of Cyclooxygenase-1 in cultured VSMC. Korean J Physiol Pharmacol. 2006; 10:161–165.
24. Gan XL, Hei ZQ, Huang HQ, Chen LX, Li SR, Cai J. Effect of Astragalus membranaceus injection on the activity of the intestinal mucosal mast cells after hemorrhagic shock-reperfusion in rats. Chin Med J (Engl). 2006; 119:1892–1898. PMID: 17134588.
25. Min YS, Lee SE, Hong ST, Kim HS, Choi BC, Sim SS, Whang WK, Sohn UD. The inhibitory effect of quercetin-3-O-beta-D-glucuronopyranoside on gastritis and reflux esophagitis in rats. Korean J Physiol Pharmacol. 2009; 13:295–300. PMID: 19885013.
26. Hozawa A, Jacobs DR Jr, Steffes MW, Gross MD, Steffen LM, Lee DH. Circulating carotenoid concentrations and incident hypertension: the Coronary Artery Risk Development in Young Adults (CARDIA) study. J Hypertens. 2009; 27:237–242. PMID: 19155781.
Article
27. Bachmann S, Mundel P. Nitric oxide in the kidney: synthesis, localization, and function. Am J Kidney Dis. 1994; 24:112–129. PMID: 7517625.
Article
28. Zalba G, San José G, Moreno MU, Fortuño MA, Fortuño A, Beaumont FJ, Díez J. Oxidative stress in arterial hypertension: role of NAD(P)H oxidase. Hypertension. 2001; 38:1395–1399. PMID: 11751724.
29. Simko F, Pechanova O, Pelouch V, Krajcirovicova K, Celec P, Palffy R, Bednarova K, Vrankova S, Adamcova M, Paulis L. Continuous light and L-NAME-induced left ventricular remodelling: different protection with melatonin and captopril. J Hypertens. 2010; 28(Suppl 1):S13–S18. PMID: 20823711.
Article
30. De Gennaro Colonna V, Rossoni G, Rigamonti A, Bonomo S, Manfredi B, Berti F, Muller E. Enalapril and quinapril improve endothelial vasodilator function and aortic eNOS gene expression in L-NAME-treated rats. Eur J Pharmacol. 2002; 450:61–66. PMID: 12176110.
Article
31. Shesely EG, Maeda N, Kim HS, Desai KM, Krege JH, Laubach VE, Sherman PA, Sessa WC, Smithies O. Elevated blood pressures in mice lacking endothelial nitric oxide synthase. Proc Natl Acad Sci U S A. 1996; 93:13176–13181. PMID: 8917564.
Article
32. John SW, Krege JH, Oliver PM, Hagaman JR, Hodgin JB, Pang SC, Flynn TG, Smithies O. Genetic decreases in atrial natriuretic peptide and salt-sensitive hypertension. Science. 1995; 267:679–681. PMID: 7839143.
Article
33. Iannone A, Rota C, Bergamini S, Tomasi A, Canfield LM. Antioxidant activity of carotenoids: an electron-spin resonance study on beta-carotene and lutein interaction with free radicals generated in a chemical system. J Biochem Mol Toxicol. 1998; 12:299–304. PMID: 9664236.
Full Text Links
  • KJPP
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr