Cardiovascular effects of high-fructose intake in rats with nitric oxide deficiency

Open access


The aim of this study was to evaluate the involvement of nitric oxide (NO) system damage in the deleterious effects of high-fructose intake in rats. Fructose was administered as 10% solution in drinking water to twelve-week-old male Wistar rats for the period of 8 weeks. Blood pressure was measured by tail-cuff plethysmography. After sacrificing the rats at the end of the treatment, relative weights of heart and liver and biochemical parameters in blood plasma were determined. Reactivity of isolated conduit arteries was measured using a force-displacement transducer for recording isometric tension. Fructose drinking rats had increased blood pressure and impaired acetylcholine-induced relaxation of the thoracic aorta in comparison with control rats drinking just tap water. Relative liver weight and plasma concentrations of glucose and triglycerides were also elevated after fructose administration. In a further group of Wistar rats, inhibition of NO production by administration of NG-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg/day) was performed throughout fructose intake. L-NAME treatment itself induces increase in blood pressure and relative heart weight as well as impairment in arterial relaxation and contractility. However, in these rats, fructose administration did not cause further elevation of blood pressure and other abnormalities observed in rats receiving fructose without L-NAME. Our results showed that in the state of NO deficiency (induced by L-NAME administration) fructose does not induce cardiovascular and metabolic alterations which develop in rats with a functional NO system. This indicates that impairment of the NO system may participate in many of the adverse effects induced by high-fructose intake.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • Beilin LJ. (1999). Lifestyle and hypertension--an overview. Clin Exp Hypertens 21: 749-762.

  • Bernatova I Puzserova A Dubovicky M. (2010). Sex diff erences in social stress-induced pressor and behavioral responses in normotensive and prehypertensive rats. Gen Physiol Biophys 29: 346-354.

  • Brands MW Garrity CA Holman MG Keen HL Alonso-Galicia M Hall JE. (1994). High-fructose diet does not raise 24-hour mean arterial pressure in rats. Am J Hypertens 7: 104-109.

  • Corry DB Eslami P Yamamoto K Nyby MD Makino H Tuck ML. (2008). Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system. J Hypertens 26: 269-275.

  • Corry DB Tuck ML. (1999). Obesity hypertension and sympathetic nervous system activity. Curr Hypertens Rep 1: 119-126.

  • D’Angelo G Elmarakby AA Pollock DM Stepp DW. (2005). Fructose feeding increases insulin resistance but not blood pressure in Sprague-Dawley rats. Hypertension 46: 806-811.

  • Dai S McNeill JH. (1995). Fructose-induced hypertension in rats is concentration- and duration-dependent. J Pharmacol Toxicol Methods 33: 101-107.

  • Dowell FJ Henrion D Duriez M Michel JB. (1996). Vascular reactivity in mesenteric resistance arteries following chronic nitric oxide synthase inhibition in Wistar rats. Br J Pharmacol 117: 341-346.

  • Elliott SS Keim NL Stern JS Teff K Havel PJ. (2002). Fructose weight gain and the insulin resistance syndrome. Am J Clin Nutr 76: 911-922.

  • Ferrari AU Daff onchio A Albergati F Bertoli P Mancia G. (1990). Intra-arterial pressure alterations during tail-cuff blood pressure measurements in normotensive and hypertensive rats. J Hypertens 8: 909-911.

  • Furchgott RF Zawadzki JV. (1980). The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288: 373-376.

  • Gardiner SM Compton AM Bennett T Palmer RM Moncada S. (1990). Regional haemodynamic changes during oral ingestion of NG-monomethyl- L-arginine or NG-nitro-L-arginine methyl ester in conscious Brattleboro rats. Br J Pharmacol 101: 10-12.

  • Gersch C Palii SP Kim KM Angerhofer A Johnson RJ Henderson GN. (2008). Inactivation of nitric oxide by uric acid. Nucleosides Nucleotides Nucleic Acids 27: 967-978.

  • Havel PJ. (2005). Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. Nutr Rev 63: 133-157.

  • Hwang IS Ho H Hoff man BB Reaven GM. (1987). Fructose-induced insulin resistance and hypertension in rats. Hypertension 10: 512-516.

  • Ignarro LJ Buga GM Wood KS Byrns RE Chaudhuri G. (1987). Endotheliumderived relaxing factor produced and released from the artery and vein is nitric oxide. Proc Natl Acad Sci USA 84: 9265-9269.

  • Johnson MD Zhang HY Kotchen TA. (1993). Sucrose does not raise blood pressure in rats maintained on a low salt intake. Hypertension 21: 779-785.

  • Johnson RJ Perez-Pozo SE Sautin YY Manitius J Sanchez-Lozada LG Feig DI Shafi u M Segal M Glassock RJ Shimada M Roncal C Nakagawa T. (2009). Hypothesis: could excessive fructose intake and uric acid cause type 2 diabetes? Endocr Rev 30: 96-116.

  • Khosla UM Zharikov S Finch JL Nakagawa T Roncal C Mu W Krotova K Block ER Prabhakar S Johnson RJ. (2005). Hyperuricemia induces endothelial dysfunction. Kidney Int 67: 1739-1742.

  • López RM Ortíz CS Ruíz A Vélez JM Castillo C Castillo EF. (2004). Impairment of smooth muscle function of rat thoracic aorta in an endotheliumindependent manner by long-term administration of N(G)-nitro-L-arginine methyl ester. Fundam Clin Pharmacol 18: 669-677.

  • Miatello R Risler N Castro C González S Rüttler M Cruzado M. (2001). Aortic smooth muscle cell proliferation and endothelial nitric oxide synthase activity in fructose-fed rats. Am J Hypertens 14: 1135-1141.

  • Monsef A. (2012). Eff ects of nitric oxide synthase inhibitor (L-NAME) on cytopathologic changes due to cholestasis in hepatic cells of adult male rats. Pol J Pathol 63: 243-247.

  • Pechánová O Bernátová I Pelouch V Babál P. (1999). L-NAME-induced protein remodeling and fi brosis in the rat heart. Physiol Res 48: 353-362.

  • Perez-Pozo SE Schold J Nakagawa T Sánchez-Lozada LG Johnson RJ Lillo JL. (2010). Excessive fructose intake induces the features of metabolic syndrome in healthy adult men: role of uric acid in the hypertensive response. Int J Obes (Lond) 34: 454-461.

  • Puzserova A Ilovska V Balis P Slezak P Bernatova I. (2014). Age-related alterations in endothelial function of femoral artery in young SHR and WKY rats. Biomed Res Int 2014: Article ID 658479 12 pages.

  • Sautin YY Nakagawa T Zharikov S Johnson RJ. (2007). Adverse eff ects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/ nitrosative stress. Am J Physiol Cell Physiol 293: C584-C596.

  • Spruss A Kanuri G Uebel K Bischoff SC Bergheim I. (2011). Role of the inducible nitric oxide synthase in the onset of fructose-induced steatosis in mice.

  • Antioxid Redox Signal 14: 2121-2135. Takagawa Y Berger ME Hori MT Tuck ML Golub MS. (2001). Long-term fructose feeding impairs vascular relaxation in rat mesenteric arteries. Am J Hypertens 14: 811-817.

  • Tappy L Le KA. (2010) Metabolic eff ects of fructose and the worldwide increase in obesity. Physiol Rev 90: 23-46.

  • Török J Zemančíková A Tabačeková M. (2012). Eff ect of high-fructose intake on cardiovascular function in normotensive and hypertensive rats. Acta Physiol 206(Suppl 693): P86.

  • Török J Holécyová A Kyselá S Bernátová I Pecháňová O. (1998). Changes in reactivity of pulmonary and systemic arteries in chronic NO-defi cient hypertension. Cardiol 7: 30-36.

  • Verma S Bhanot S McNeill JH. (1994). Antihypertensive eff ects of metformin in fructose-fed hyperinsulinemic hypertensive rats. J Pharmacol Exp Ther 271: 1334-1337.

  • Yoneyama T Ohkawa S Watanabe T Odamaki M Kumagai H Kimura M Hishida A. (1998). The contribution of nitric oxide to renal vascular wall thickening in rats with L-NAME-induced hypertension. Virchows Arch 433: 549-557.

  • Zemančíková A Török J. (2013). Diminished contractile responses of isolated conduit arteries in two rat models of hypertension. Chin J Physiol 56: 230-235.

  • Zharikov S Krotova K Hu H Baylis C Johnson RJ Block ER Patel J. (2008). Uric acid decreases NO production and increases arginase activity in cultured pulmonary artery endothelial cells. Am J Physiol Cell Physiol 295: C1183-C1190.

Journal information
Impact Factor

CiteScore 2018: 1.78

SCImago Journal Rank (SJR) 2018: 0.274
Source Normalized Impact per Paper (SNIP) 2018: 0.671

Cited By
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 350 204 7
PDF Downloads 230 136 3