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D-Carvone, a Monoterpene Reverses Alterations in Heart Rate, Nitric Oxide, Aortic Lipids and Enzymatic Antioxidant Status in Nitric Oxide Deficient Hypertensive Rats

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The present study was aimed to assess the antihyperlipidemic, antihypertensive and antioxidant effect of D-carvone, a monoterpene against Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME) induced hypertension. Hypertension was prompted in adult male albino rats of the Wistar strain by oral administration of the L-NAME (40 mg/kg body weight) in drinking water for 4 weeks. Rats were treated with D-carvone (5, 10 and 20 mg/kg body weight) for four weeks. L-NAME treated rats exhibited significant increase in water intake, heart rate, aortic lipids level such as triglycerides (TG), total cholesterol (TC), free fatty acids (FFA) and significant decrease in the level of phospholipids (PL), plasma nitric oxide (NO). The activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were decreased in erythrocytes of L-NAME induced hypertensive rats. Treatment with D-carvone restored all the above parameters to near normal level. These results suggest that D-carvone acts as an antihyperlipidemic, antihypertensive and antioxidant agent against L-NAME induced hypertensive rats.


International Letters of Natural Sciences (Volume 32)
T. Rajeshwari and B. Raja, "D-Carvone, a Monoterpene Reverses Alterations in Heart Rate, Nitric Oxide, Aortic Lipids and Enzymatic Antioxidant Status in Nitric Oxide Deficient Hypertensive Rats", International Letters of Natural Sciences, Vol. 32, pp. 19-31, 2015
Online since:
Jan 2015

[1] Attia DM, Verhagen AM, Stroes ES. Vitamin E alleviates renal injury, but not hypertension, during chronic nitric oxide synthase inhibition in rats. J. Am. Soc. Nephrol. 2001; 12: 2585–2593.

[2] Beswick RA, Dorrance AM, Romulo Leite RC. NADH/NADPH oxidase and enhanced superoxide production in the mineralocorticoid hypertensive rat. Hypertension 2001; 38: 1107–1111.

DOI: 10.1161/hy1101.093423

[3] Boulanger CM. Secondary endothelial dysfunction: hypertension and heart failure. Journal of Molecular and Cellular Cardiology 1999; 31: 39-49.

DOI: 10.1006/jmcc.1998.0842

[4] Casazza K, Natour N, Divers J, Vaughan LK, Bigham AW, Gower BA, et al. Triglyceride concentration is independently associated with variation in the LPL gene in african american and european american women, Open Obes. J. 2009; 1: 23-31.

DOI: 10.2174/1876823700901010023

[5] Chang T, Wu L. Methylglyoxal, oxidative stress and hypertension. Canadian Journal of Physiology and Pharmacology 2006; 84: 1229-38.

[6] De Gennaro Colonn a V, Rigamonti A, Fioretti S, Bo-nomo S, Manfredi B, Ferrario P. Angiotensin-converting enzyme inhibition and angiotensin AT1-receptor antagonism equally improve endothelial vasodilator function in L-NAME-induced hypertensive rats. Eur. J. Pharmacol. 2005; 516: 253 –259.

DOI: 10.1016/j.ejphar.2005.04.004

[7] Dias-Junior CA, Cau SB, Tanus-Santos JE. Role of nitric oxide in the control of the pulmonary circulation: physiological, pathophysiological, and therapeutic implications. J Bras Pneumol 2008; 34: 412-419.

[8] Diebolt M, Bucher B and Andriantsitohaina R. Wine polyphenols decrease blood pressure, improve NO vasodilatation, and induce gene expression. Hypertension. 2001; 38(2): 159-165.

DOI: 10.1161/01.hyp.38.2.159

[9] Dryden GW Jr, Deaciuc I, Arteel G, McClain CJ. Clinical implications of oxidative stress and antioxidant therapy, Curr. Gastroenterol. Rep. 2005; 7: 308-316.

DOI: 10.1007/s11894-005-0024-y

[10] Falholt K, Lund B, Falholt W. An easy colorimetric micro method for routine determination of free fatty acids in plasma. Clin. Chim. Acta. 1973; 46, 105–1.

DOI: 10.1016/0009-8981(73)90016-8

[11] Folch J, Lees M, Sloane Stanly GH. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1957; 226: 497-509.

[12] Fossati P, Prencipe L. Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clin. Chem 1982; 28: 2077–80.

[13] Friedwald WT, Levy RJ, Fredricken DS. Estimation of the concentration of LDL cholesterol in the plasma without the use of preparative ultracentrifuge. Clin. Chem. 1972b; 18: 499–502.

[14] Friedwald WT, Levy RJ, Fredricken DS. Estimation of VLDL-cholesterol in the plasma without the use of preparative ultracentrifuge. Clin. Chem. 1972a; 18, 449.

[15] Grassi D, Lippi C, Necozione S, Desideri G and Ferri C. Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. The American Journal of Clinical Nutrition. 2005; 81 (3): 611-614.

[16] Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR. Analysis of nitrate, nitrite, and [15 N] nitrate in biological fluids. Anal Biochem 1982; 126: 131–8.

DOI: 10.1016/0003-2697(82)90118-x

[17] Gu D, Reynolds K, Wu X, Chen J, Duan X, Muntner P, Huang G, Reynolds RF, Su S, Whelton PK, He J. Prevalence, awareness, treatment, and control of hypertension in china. Hypertension 2002; 40: 920–927.

DOI: 10.1161/01.hyp.0000040263.94619.d5

[18] Johri RK. Cuminumcyminum and Carumcarvi: An update. Pharmacogn Rev 2011; 5: 63-72.

[19] Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 1984; 21: 130-132.

[20] Khedara A, Kawai Y, Kayashita K, Kat N. Feedeing rats the nitric oxide synthase inhibitor, L-Nω nitro arginine, elevates serum triglyceride and cholesterol and lowers hepatic fatty acid oxidation,J. Nutr. 1996; 126: 2563-2567.

[21] Kumar S, Prahalathan P, Raja B. Antihypertensive and antioxidant potential of vanillic acid, a phenolic compound in L-NAME induced hypertensive rats: a dose-dependence study. Redox Report 2011; 16: 208-215.

DOI: 10.1179/1351000211y.0000000009

[22] Kumar S, Saravanakumar M, Raja B. Efficacy of piperine, an alkaloidal constituent of pepper on nitric oxide, antioxidants and lipid peroxidation markers in L-NAME induced hypertensive rats. Int J Res Pharm Sci 2010; 1: 300-307.

[23] Li H, Xie YH, Yang Q, Wang SW, Zhang BL, et al. Cardioprotective effect of paeonol and danshensu combination on isoproterenol-induced myocardial injury in rats, PLoS ONE. 2012; doi: 10. 1371/journal. pone. 0048872.

DOI: 10.1371/journal.pone.0048872

[24] Mates JM, Sanchez-Jimenez F. Antioxidant enzymes and their implications in pathophysiologic processes. Frontiers in Bioscience 1999; 4: 339-345.

[25] Mayes PA, Metabolism of Lipids, In: Harper HA, Rodwell VW, Mayes PA, Reviews of physiological chemistry, Lange publications, LosAltos, 1997; 280-321.

[26] Moncada S, Higgs A. The L-arginine– nitric oxid e pathway. N. Engl. J. Med. 1993; 329: 2002–(2012).

[27] Muruganathan U, Srinivasan S, Indumathi D. Antihyperglycemic effect of carvone: Effect on the levels of glycoprotein components in streptozotocin-induced diabetic rats. Journal of Acute Disease. doi: 10. 1016/S2221-6189(13)60150-X.

DOI: 10.1016/s2221-6189(13)60150-x

[28] Nguelefack-Mbuyoa PE, Nguelefackb TB, Dongmoc B, Afkird S, Azebazee AGB, Dimoa T, Legssyerd A, Kamanyi A, Ziyyat A. Anti hypertensive effects of the methanol/methylene chloride stem bark extract of mammea africana in L-NAME-induced hypertensive rats. Journal of Ethnopharmacology 2008; 117: 446–450.

DOI: 10.1016/j.jep.2008.02.028

[29] Palmieri VO, Grattagliano I, Portincasa P. Systemic oxidative alterations are associated with visceral adiposity and liver steatosis in patients with metabolic syndrome. J Nutr 2006; 136: 3022–26.

[30] Rajeshkumar NV, Kuttan R. Modulation of carcinogenic response and antioxidant enzymes of rats administered with 1, 2-dimethylhydrazine by Picroliv, Cancer Lett. 2003; 191: 137-43.

DOI: 10.1016/s0304-3835(02)00203-3

[31] Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Science 1973; 179: 588-590.

DOI: 10.1126/science.179.4073.588

[32] Rybka J, Kupczyk D, Kcdziora-Kornatowska K, et al. Glutathione related antioxidant defense system in elderly patients treated for hypertension. Cardiovascular Toxicology 2011; 11: 1-9.

DOI: 10.1007/s12012-010-9096-5

[33] Saravana kumar M, Kumar S, Raja B. Antihypertensive and antioxidant potential of borneol-a natural terpene in L-NAME induced hypertensive rats. Int. J. Pharm and Biol Arch. 2010; 1: 271-279.

[34] Saravanakumar M, Raja B. Effect of veratric acid on the cardiovascular risk of L-NAME–induced hypertensive rats,J. Cardiovasc. Pharmacol. 2012; 59: 553-562.

DOI: 10.1097/fjc.0b013e31824f9174

[35] Saravanakumar M, Raja B. Veratric acid, a phenolic acid attenuates blood pressure and oxidative stress in L-NAME induced hypertensive rats. Eur J Pharmacol 2011; 671: 87-94.

DOI: 10.1016/j.ejphar.2011.08.052

[36] Sinha AK. Colorimetric assay of catalase. Anal Biochem 1972; 47: 389-394.

[37] Thakali K, Davenport L, Fink GD, Watts WS. Pleiotropic effects of hydrogen peroxide in arteries and veins from normotensive and hypertensive rats. Hypertension 2006; 47: 482–487.

DOI: 10.1161/01.hyp.0000201540.91234.8f

[38] Vinothkumar R, Sudha M, Viswanathan P, Kabalimoorthy J, Balasubramanian T, Nalini N. Modulating effect of D-carvone on 1, 2-dimethylhydrazine induced preneoplastic lesions, oxidative stress and biotransforming enzymes in an experimental model of rat colon carcinogenesis. Cell Proliferation 2013; 46: 705-720.

DOI: 10.1111/cpr.12062

[39] Whitworth JA. World Health Organization, International Society of Hypertension Writing Group. 2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens 2003; 21: 1983‑92.

DOI: 10.1097/00004872-200311000-00002

[40] Wong ND, Lopez V, Tang S, Williams GR. Prevalence, treatment, and control of combined hypertension and hypercholesterolemia in the United States. Am J Cardiol 2006; 98: 204–8.

[41] Yang Y, Li JX, Chen JC, Cao J, Lu XF, Chen SF, et al. Effect of elevated total cholesterol level and hypertension on the risk of fatal cardiovascular disease: a cohort study of Chinese steel workers, Chin. Med. J. (Engl). 2011; 124: 3702-3706.

[42] Zilversmit DB, Davis AK. Micro determination of plasma phospholipids by trichloroacetic acid precipitation. J. Lab. Clin. Med. 1950; 35: 155-60.

[43] Zlatkis A, Zak B, Boyle AJ. A new method for the direct determination of serum cholesterol. J. Lab. Clin. Med 1953; 41: 486–92. ( Received 22 December 2014; accepted 30 December 2014 ).

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