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Quercetin restores plasma nitrite and nitroso species levels in renovascular hypertension

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Abstract

Quercetin has antioxidants properties which may increase nitric oxide (NO) bioavailability. However, the effects of quercetin on NO status have been poorly studied. We evaluated whether quercetin improves the plasma levels of NO metabolites in two-kidney one-clip (2K1C) hypertensive rats and assessed its effect on endothelial function. Sham-operated and 2K1C rats were treated with quercetin (10 mg−1 kg−1 day−1 by gavage) or vehicle for 3 weeks. Systolic blood pressure (SBP) was monitored weekly. Vascular responses to acetylcholine (Ach) and sodium nitroprusside (SNP) were assessed in hindquarter vascular bed. Plasma nitrate levels were assessed by Griess reagent and plasma nitrite and nitroso species (S, N-nitroso species) were assessed by ozone- based chemiluminescence. Aortic NADPH oxidase activity and superoxide production were evaluated. While quercetin had no effects in control normotensive rats (P > 0.05), it significantly reduced SBP in 2K1C rats (P < 0.05). At the end of treatment, plasma nitrate levels were similar in all experimental groups (P > 0.05). However, plasma nitrite and the nitroso species levels were significantly lower in 2K1C rats when compared with controls (P < 0.05). Quercetin treatment restored plasma nitrite and nitroso species levels to those found in the sham-vehicle group (P < 0.05). While quercetin treatment induced no significant changes in responses to SNP (P > 0.05), it restored the vascular responses to Ach. Quercetin significantly attenuated 2K1C-hypertension-induced increases in NADPH oxidase activity and vascular superoxide production (P < 0.05). These results suggest that the antihypertensive effects of quercetin were associated with increased NO formation and improved endothelial function, which probably result from its antioxidant effects.

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References

  • Cai H, Harrison DG (2000) Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 87:840–844

    CAS  PubMed  Google Scholar 

  • Castro MM, Rizzi E, Figueiredo-Lopes L, Fernandes K, Bendhack LM, Pitol DL, Gerlach RF, Tanus-Santos JE (2008) Metalloproteinase inhibition ameliorates hypertension and prevents vascular dysfunction and remodeling in renovascular hypertensive rats. Atherosclerosis 198:320–331

    Article  CAS  PubMed  Google Scholar 

  • Ceron CS, Castro MM, Rizzi E, Montenegro MF, Fontana V, Salgado MC, Gerlach RF, Tanus-Santos JE (2010) Spironolactone and hydrochlorothiazide exert antioxidant effects and reduce vascular matrix metalloproteinase-2 activity and expression in a model of renovascular hypertension. Br J Pharmacol 160:77–87

    Article  CAS  PubMed  Google Scholar 

  • Dias-Junior CA, Gladwin MT, Tanus-Santos JE (2006) Low-dose intravenous nitrite improves hemodynamics in a canine model of acute pulmonary thromboembolism. Free Radic Biol Med 41:1764–1770

    Article  CAS  PubMed  Google Scholar 

  • Duarte J, Perez-Palencia R, Vargas F, Ocete MA, Perez-Vizcaino F, Zarzuelo A, Tamargo J (2001) Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats. Br J Pharmacol 133:117–124

    Article  CAS  PubMed  Google Scholar 

  • Duarte J, Jimenez R, O’Valle F, Galisteo M, Perez-Palencia R, Vargas F, Perez-Vizcaino F, Zarzuelo A, Tamargo J (2002) Protective effects of the flavonoid quercetin in chronic nitric oxide deficient rats. J Hypertens 20:1843–1854

    Article  CAS  PubMed  Google Scholar 

  • Edwards RL, Lyon T, Litwin SE, Rabovsky A, Symons JD, Jalili T (2007) Quercetin reduces blood pressure in hypertensive subjects. J Nutr 137:2405–2411

    CAS  PubMed  Google Scholar 

  • Feelisch M, Rassaf T, Mnaimneh S, Singh N, Bryan NS, Jourd’Heuil D, Kelm M (2002) Concomitant s-, n-, and heme-nitros(yl)ation in biological tissues and fluids: implications for the fate of no in vivo. FASEB J 16:1775–1785

    Article  CAS  PubMed  Google Scholar 

  • Galisteo M, Garcia-Saura MF, Jimenez R, Villar IC, Wangensteen R, Zarzuelo A, Vargas F, Duarte J (2004a) Effects of quercetin treatment on vascular function in deoxycorticosterone acetate-salt hypertensive rats. Comparative study with verapamil. Planta Med 70:334–341

    Article  CAS  PubMed  Google Scholar 

  • Galisteo M, Garcia-Saura MF, Jimenez R, Villar IC, Zarzuelo A, Vargas F, Duarte J (2004b) Effects of chronic quercetin treatment on antioxidant defence system and oxidative status of deoxycorticosterone acetate-salt-hypertensive rats. Mol Cell Biochem 259:91–99

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Saura MF, Galisteo M, Villar IC, Bermejo A, Zarzuelo A, Vargas F, Duarte J (2005) Effects of chronic quercetin treatment in experimental renovascular hypertension. Mol Cell Biochem 270:147–155

    Article  CAS  PubMed  Google Scholar 

  • Harrison DG, Gongora MC (2009) Oxidative stress and hypertension. Med Clin North Am 93:621–635

    Article  CAS  PubMed  Google Scholar 

  • Heiss C, Lauer T, Dejam A, Kleinbongard P, Hamada S, Rassaf T, Matern S, Feelisch M, Kelm M (2006) Plasma nitroso compounds are decreased in patients with endothelial dysfunction. J Am Coll Cardiol 47:573–579

    Article  CAS  PubMed  Google Scholar 

  • Kleinbongard P, Dejam A, Lauer T, Rassaf T, Schindler A, Picker O, Scheeren T, Godecke A, Schrader J, Schulz R, Heusch G, Schaub GA, Bryan NS, Feelisch M, Kelm M (2003) Plasma nitrite reflects constitutive nitric oxide synthase activity in mammals. Free Radic Biol Med 35:790–796

    Article  CAS  PubMed  Google Scholar 

  • Kleinbongard P, Dejam A, Lauer T, Jax T, Kerber S, Gharini P, Balzer J, Zotz RB, Scharf RE, Willers R, Schechter AN, Feelisch M, Kelm M (2006) Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humans. Free Radic Biol Med 40:295–302

    Article  CAS  PubMed  Google Scholar 

  • Kuhlmann CR, Schaefer CA, Kosok C, Abdallah Y, Walther S, Ludders DW, Neumann T, Tillmanns H, Schafer C, Piper HM, Erdogan A (2005) Quercetin-induced induction of the no/cgmp pathway depends on ca2+-activated k+ channel-induced hyperpolarization-mediated ca2+-entry into cultured human endothelial cells. Planta Med 71:520–524

    Article  CAS  PubMed  Google Scholar 

  • Lauer T, Preik M, Rassaf T, Strauer BE, Deussen A, Feelisch M, Kelm M (2001) Plasma nitrite rather than nitrate reflects regional endothelial nitric oxide synthase activity but lacks intrinsic vasodilator action. Proc Natl Acad Sci USA 98:12814–12819

    Article  CAS  PubMed  Google Scholar 

  • Loke WM, Hodgson JM, Proudfoot JM, McKinley AJ, Puddey IB, Croft KD (2008) Pure dietary flavonoids quercetin and (−)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men. Am J Clin Nutr 88:1018–1025

    CAS  PubMed  Google Scholar 

  • Lopez-Lopez G, Moreno L, Cogolludo A, Galisteo M, Ibarra M, Duarte J, Lodi F, Tamargo J, Perez-Vizcaino F (2004) Nitric oxide (no) scavenging and no protecting effects of quercetin and their biological significance in vascular smooth muscle. Mol Pharmacol 65:851–859

    Article  CAS  PubMed  Google Scholar 

  • MacArthur PH, Shiva S, Gladwin MT (2007) Measurement of circulating nitrite and s-nitrosothiols by reductive chemiluminescence. J Chromatogr B Analyt Technol Biomed Life Sci 851:93–105

    Article  CAS  PubMed  Google Scholar 

  • Mackraj I, Govender T, Ramesar S (2008) The antihypertensive effects of quercetin in a salt-sensitive model of hypertension. J Cardiovasc Pharmacol 51:239–245

    Article  CAS  PubMed  Google Scholar 

  • Martinez ML, Castro MM, Rizzi E, Fernandes K, Demacq C, Bendhack LM, Gerlach RF, Tanus-Santos JE (2008) Lercanidipine reduces matrix metalloproteinase-2 activity and reverses vascular dysfunction in renovascular hypertensive rats. Eur J Pharmacol 591:224–230

    Article  CAS  PubMed  Google Scholar 

  • Metzger IF, Sertorio JT, Tanus-Santos JE (2006) Relationship between systemic nitric oxide metabolites and cyclic gmp in healthy male volunteers. Acta Physiol (Oxf) 188:123–127

    Article  CAS  Google Scholar 

  • Metzger IF, Sertorio JT, Tanus-Santos JE (2007) Modulation of nitric oxide formation by endothelial nitric oxide synthase gene haplotypes. Free Radic Biol Med 43:987–992

    Article  CAS  PubMed  Google Scholar 

  • Montenegro MF, Pessa LR, Gomes VA, Desta Z, Flockhart DA, Tanus-Santos JE (2009) Assessment of vascular effects of tamoxifen and its metabolites on the rat perfused hindquarter vascular bed. Basic Clin Pharmacol Toxicol 104:400–407

    Article  CAS  PubMed  Google Scholar 

  • Perez-Vizcaino F, Duarte J, Jimenez R, Santos-Buelga C, Osuna A (2009) Antihypertensive effects of the flavonoid quercetin. Pharmacol Rep 61:67–75

    CAS  PubMed  Google Scholar 

  • Sanchez M, Galisteo M, Vera R, Villar IC, Zarzuelo A, Tamargo J, Perez-Vizcaino F, Duarte J (2006) Quercetin downregulates nadph oxidase, increases enos activity and prevents endothelial dysfunction in spontaneously hypertensive rats. J Hypertens 24:75–84

    Article  CAS  PubMed  Google Scholar 

  • Sanchez M, Lodi F, Vera R, Villar IC, Cogolludo A, Jimenez R, Moreno L, Romero M, Tamargo J, Perez-Vizcaino F, Duarte J (2007) Quercetin and isorhamnetin prevent endothelial dysfunction, superoxide production, and overexpression of p47phox induced by angiotensin ii in rat aorta. J Nutr 137:910–915

    CAS  PubMed  Google Scholar 

  • Sandrim VC, Montenegro MF, Palei AC, Metzger IF, Sertorio JT, Cavalli RC, Tanus-Santos JE (2010) Increased circulating cell-free hemoglobin levels reduce nitric oxide bioavailability in preeclampsia. Free Radic Biol Med 49:493–500

    Article  CAS  PubMed  Google Scholar 

  • Schulz E, Jansen T, Wenzel P, Daiber A, Munzel T (2008) Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension. Antioxid Redox Signal 10:1115–1126

    Article  CAS  PubMed  Google Scholar 

  • Sedeek M, Hebert RL, Kennedy CR, Burns KD, Touyz RM (2009) Molecular mechanisms of hypertension: role of nox family nadph oxidases. Curr Opin Nephrol Hypertens 18:122–127

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto Y, Oue E (2006) Antihypertensive effect of quercetin in rats fed with a high-fat high-sucrose diet. Biosci Biotechnol Biochem 70:933–939

    Article  CAS  PubMed  Google Scholar 

  • Zhao XY, Gu ZL (1996) Effects of quercetin on production and release of endothelin and cgmp from cultured endothelial cells. Zhongguo Yao Li Xue Bao 17:442–444

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was funded by the Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP-Brazil) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-Brazil). The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Faculty of Medicine of Ribeirao Preto, Department of Pharmacology, University of São Paulo, Av. Bandeirantes, 3900, 14049-900, Ribeirao Preto, São Paulo, Brazil

    Marcelo F. Montenegro, Evandro M. Neto-Neves, Carla S. Ceron, Michele M. Castro, Alexandre Kanashiro & Jose E. Tanus-Santos

  2. Campus Centro-Oeste Dona Lindu, Department of Pharmacology, Federal University of São João Del Rei, Rua Sebastiao Goncalves Coelho, 400, 35501-296, Divinopolis, Minas Gerais, Brazil

    Carlos A. Dias-Junior

  3. Faculty of Medical Sciences, Department of Pharmacology, State University of Campinas, 13081-970, Campinas, São Paulo, Brazil

    Valeria A. Gomes

Authors
  1. Marcelo F. Montenegro
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  2. Evandro M. Neto-Neves
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  3. Carlos A. Dias-Junior
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  4. Carla S. Ceron
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  5. Michele M. Castro
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  6. Valeria A. Gomes
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  8. Jose E. Tanus-Santos
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Correspondence to Jose E. Tanus-Santos.

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Montenegro, M.F., Neto-Neves, E.M., Dias-Junior, C.A. et al. Quercetin restores plasma nitrite and nitroso species levels in renovascular hypertension. Naunyn-Schmied Arch Pharmacol 382, 293–301 (2010). https://doi.org/10.1007/s00210-010-0546-1

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  • DOI: https://doi.org/10.1007/s00210-010-0546-1

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