Skip to main content
SpringerLink
Log in

Acute administration of single oral dose of grape seed polyphenols restores blood pressure in a rat model of metabolic syndrome: role of nitric oxide and prostacyclin

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

The aims of this study were to evaluate the antihypertensive effectiveness of different doses of grape seed polyphenols in cafeteria diet-fed hypertensive rats (CHRs) and to establish the mechanism involved in the blood pressure (BP) lowering effect of these compounds in this experimental model of metabolic syndrome (MS).

Methods

Male 8-week-old Wistar rats were fed cafeteria or standard (ST) diet for 10 weeks. After this, the antihypertensive effect of a single oral administration of a polyphenol grape seed extract (GSPE) was tested at different doses (250, 375 and 500 mg/kg) in CHRs. BP was recorded before and 2, 4, 6, 8, 24 and 48 h post-administration. The hypotensive effect of GSPE was also proved in ST diet-fed rats. Additionally, in other experiment, CHRs were orally administered 375 mg/kg GSPE. Four hours post-administration, the rats were intraperitoneally administrated 30 mg/kg NG-nitro-l-arginine methyl ester (l-NAME) or 5 mg/kg indomethacin [inhibitors of nitric oxide (NO) and prostacyclin synthesis, respectively]. BP was recorded initially and 6 h post-administration.

Results

GSPE produced a decrease in SBP and DBP, the most effective dose (375 mg/kg) showing an antihypertensive effect in CHRs similar to the drug captopril, and did not affect BP of ST diet-fed rats. The antihypertensive effect was completely abolished by l-NAME and partially inhibited by indomethacin.

Conclusions

GSPE acts as an antihypertensive agent in a rat model of hypertension associated with MS. The change in endothelium-derived NO availability is one of the mechanisms involved in the antihypertensive effect of GSPE in CHRs. Additionally, endothelial prostacyclin contributes to the effect of GSPE on arterial BP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Papadogiannis DE, Protogerou AD (2010) Blood pressure variability: a confounder and a cardiovascular risk factor. Hypertens Res 34:162–163. doi:10.1038/hr.2010.223

    Article  Google Scholar 

  2. Collins R, Peto R, MacMahon S, Godwin J, Qizilbash N, Hebert P, Eberlein KA, Taylor JO, Hennekens CH, Fiebach NH (1990) Blood pressure, stroke, and coronary heart disease: part 2, short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 335:827–838

    Article  CAS  Google Scholar 

  3. Isezuo SA, Badung SLH, Omotoso ABO (2003) Comparative analysis of lipid profiles among patients with type 2 diabetes mellitus, hypertension and concurrent type 2 diabetes, and hypertension: a view of metabolic syndrome. J Natl Med Assoc 95:328–334

    CAS  Google Scholar 

  4. Sampey BP, Vanhoose AM, Winfield HM, Freemerman AJ, Muehlbauer MJ, Fueger PT, Newgard CB, Makowski L (2011) Cafeteria diet is a robust model of human metabolic syndrome with liver and adipose inflammation: comparison to high-fat diet. Obesity 19:1109–1117. doi:10.1038/oby.2011.18

    Article  CAS  Google Scholar 

  5. Redon J, Cifkova R, Laurent S, Nilsson P, Narkiewicz K, Erdine S, Mancia G (2008) The metabolic syndrome in hypertension: European society of hypertension position statement. J Hypertens 26:1891–1900. doi:10.1097/HJH.0b013e328302ca38

    Article  CAS  Google Scholar 

  6. Panchal SK, Brown L (2010) Rodent models for metabolic syndrome research. J Biomed Biotechnol 2011:351982. doi:10.1155/2011/351982

    Google Scholar 

  7. Coatmellec-Taglioni G, Dausse JP, Giudicelli Y, Ribière C (2003) Sexual dimorphism in cafeteria diet-induced hypertension is associated with gender-related difference in renal leptin receptor down-regulation. J Pharmacol Exp Ther 305:362–367

    Article  CAS  Google Scholar 

  8. Pons Z, Guerrero L, Margalef M, Arola L, Arola-Arnal A, Muguerza B (2014) Effect of low molecular grape seed proanthocyanidins on blood pressure and lipid homeostasis in cafeteria diet-fed rats. J Physiol Biochem 70:629–637. doi:10.1007/s13105-014-0329-0

    Article  CAS  Google Scholar 

  9. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S (2007) 2007 Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 28:1462–1536. doi:10.1093/eurheartj/ehm236

    Google Scholar 

  10. Cienfuegos-Jovellanos E, Quiñones M, Muguerza B, Moulay L, Miguel M, Aleixandre A (2009) Antihypertensive effect of a polyphenol-rich cocoa powder industrially processed to preserve the original flavonoids of the cocoa beans. J Agric Food Chem 57:6156–6162. doi:10.1021/jf804045b

    Article  CAS  Google Scholar 

  11. Quiñones M, Miguel M, Muguerza B, Aleixandre A (2011) Effect of a cocoa polyphenol extract in spontaneously hypertensive rats. Food Funct 2:649–653. doi:10.1039/c1fo10119f

    Article  Google Scholar 

  12. Quiñones M, Guerrero L, Suarez M, Pons Z, Aleixandre A, Arola L, Muguerza B (2013) Low-molecular procyanidin rich grape seed extract exerts antihypertensive effect in males spontaneously hypertensive rats. Food Res Int 51:587–595. doi:10.1016/j.foores.2013.01.023

    Article  Google Scholar 

  13. Quiñones M, Muguerza B, Miguel M, Aleixandre A (2011) Evidence that nitric oxide mediates the blood pressure lowering effect of a polyphenol-rich cocoa powder in spontaneously hypertensive rats. Pharmacol Res 64:478–481. doi:10.1016/j.phrs.2011.06.005

    Article  Google Scholar 

  14. Quiñones M, Guerrero L, Fernandez-Vallinas S, Pons Z, Arola L, Aleixandre A, Muguerza B (2014) Involvement of nitric oxide and prostacyclin in the antihypertensive effect of low-molecular-weight procyanidin rich grape seed extract in male spontaneously hypertensive rats. J Funct Foods 6:419–427. doi:10.1016/j.jff.2013.11.008

    Article  Google Scholar 

  15. Singleton VL, Rossi JA (1965) Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am J Enol Vitic 16:144–158 citeulike-article-id:7170825

    CAS  Google Scholar 

  16. Suárez M, Romero MP, Macià A, Valls RM, Fernández S, Solà R, Motilva MJ (2009) Improved method for identifying and quantifying olive oil phenolic compounds and their metabolites in human plasma by microelution solid-phase extraction plate and liquid chromatography–tandem mass spectrometry. J Chromatogr B 877:4097–4106. doi:10.1016/j.jchromb.2009.10.025

    Article  Google Scholar 

  17. Buñag RD (1973) Validation in awake rats of a tail-cuff method for measuring systolic pressure. J Appl Physiol 34:279–282

    Google Scholar 

  18. Cordero A, Moreno J, Alegría E (2006) Hipertensión arterial y síndrome metabólico. Rev Española Cardiol Supl 5:38D–45D. doi:10.1016/S1131-3587(05)74119-4

    Article  Google Scholar 

  19. Quiñones M, Sánchez D, Muguerza B, Moulay L, Laghi S, Miguel M, Aleixandre A (2010) Long-term intake of CocoanOX attenuates the development of hypertension in spontaneously hypertensive rats. Food Chem 122:1013–1019. doi:10.1016/j.foodchem.2010.03.059

    Article  Google Scholar 

  20. Mancia G, Fagard R, Narkiewicz K, Redón J, Zanchetti A, Böhm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM et al (2013) 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 31:1281–1357. doi:10.1097/01.hjh.0000431740.32696.cc

    Article  CAS  Google Scholar 

  21. Cedó L, Castell-Auví A, Pallarès V, Blay M, Ardévol A, Pinent M (2013) Grape seed procyanidin extract improves insulin production but enhances Bax protein expression in cafeteria-treated male rats. Int J Food Sci 2013:875314. doi:10.1155/2013/875314

    Article  Google Scholar 

  22. Procházková D, Bousova I, Wilhelmová N (2011) Antioxidant and prooxidant properties of flavonoids. Fitoterapia 82:513–523. doi:10.1016/j.fitote.2011.01.018

    Article  Google Scholar 

  23. Touyz RM (2004) Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension what is the clinical significance? Hypertension 44:248–252. doi:10.1161/01.HYP.0000138070.47616.9d

    Article  CAS  Google Scholar 

  24. Actis-Goretta L, Ottaviani JI, Keen CL, Fraga CG (2003) Inhibition of angiotensin converting enzyme (ACE) activity by flavan-3-ols and procyanidins. FEBS Lett 555:597–600

    Article  CAS  Google Scholar 

  25. Actis-Goretta L, Ottaviani JI, Fraga CG (2006) Inhibition of angiotensin converting enzyme activity by flavanol-rich foods. J Agric Food Chem 54:229–234

    Article  CAS  Google Scholar 

  26. Guerrero L, Castillo J, Quiñones M, Garcia-Vallvé S, Arola L, Pujadas G, Muguerza B (2012) Inhibition of angiotensin-converting enzyme activity by flavonoids: structure–activity relationship studies. PLoS One 7:e49493

    Article  CAS  Google Scholar 

  27. Ottaviani JI, Actis-Goretta L, Villordo JJ, Fraga CG (2006) Procyanidin structure defines the extent and specificity of angiotensin I converting enzyme inhibition. Biochimie 88:359–365

    Article  CAS  Google Scholar 

  28. Persson IAL, Persson K, Hägg S, Andersson RGG (2011) Effects of cocoa extract and dark chocolate on angiotensin-converting enzyme and nitric oxide in human endothelial cells and healthy volunteers—a nutrigenomics perspective. J Cardiovasc Pharmacol 57:44–50

    Article  CAS  Google Scholar 

  29. Tesauro M, Cardillo C (2011) Obesity, blood vessels and metabolic syndrome. Acta Physiol 203:279–286. doi:10.1111/j.1748-1716.2011.02290.x

    Article  CAS  Google Scholar 

  30. Sekiguchi F, Yanamoto A, Sunano S (2004) Superoxide dismutase reduces the impairment of endothelium-dependent relaxation in the spontaneously hypertensive rat aorta. J Smooth Muscle Res 40:65–74. doi:10.1540/jsmr.40.65

    Article  Google Scholar 

  31. Dobrian AD, Davies MJ, Schriver SD, Lauterio TJ, Prewitt RL (2001) Oxidative stress in a rat model of obesity-induced hypertension. Hypertension 37:554–560. doi:10.1161/01.HYP.37.2.554

    Article  CAS  Google Scholar 

  32. Rees DD, Schulz R, Hodson HF, Palmer RMJ, Moncada S (1990) Identification of some novel inhibitors of the vascular nitric oxide synthase in vivo and in vitro. Nitric oxide from l-arginine a bioregulatory Syst. In: Proceedings of a symposium held at the Royal Society of London, Elsevier, Amsterdam, pp 485–487

  33. Vane JR, Gryglewski RJ, Botting RM (1987) The endothelial cell as a metabolic and endocrine organ. Trends Pharmacol Sci 8:491–496. doi:10.1016/0165-6147(87)90045-9

    Article  CAS  Google Scholar 

  34. Schramm DD, Wang JF, Holt RR, Ensunsa JL, Gonsalves JL, Lazarus SA, Schmitz HH, German JB, Keen CL (2001) Chocolate procyanidins decrease the leukotriene-prostacyclin ratio in humans and human aortic endothelial cells. Am J Clin Nutr 73:36–40

    CAS  Google Scholar 

  35. Maffei R, Carini M, Aldini G, Berti F, Rossoni G, Bombardelli E, Morazzoni P (1999) Diet enriched with procyanidins enhances antioxidant activity and reduces myocardial post-ischaemic damage in rats. Life Sci 64:627–642. doi:10.1016/S0024-3205(98)00605-5

    Article  Google Scholar 

Download references

Acknowledgments

This work has been supported by Grant No. AGL2013-40707-RI from the Spanish Government. We want to thank Niuka Llópiz, Rosa Pastor and Yaiza Tobajas for their technical support and to Matthew Cox for the language revision of the article.

Conflict of interest

The authors declare no conflict of interest.

Author information

Authors and Affiliations

  1. Nutrigenomic Research Group, Biochemistry and Biotechnology Department, Universitat Rovira i Virgili, C/Marcel.lí Domingo, 43007, Tarragona, Spain

    Zara Pons, Maria Margalef, Francisca I. Bravo, Anna Arola-Arnal & Begoña Muguerza

  2. Centre Tecnològic de Nutrició i Salut (CTNS), TECNIO, CEICS, Tarragona, Spain

    Begoña Muguerza

Authors
  1. Zara Pons
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Margalef
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francisca I. Bravo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anna Arola-Arnal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Begoña Muguerza
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anna Arola-Arnal.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pons, Z., Margalef, M., Bravo, F.I. et al. Acute administration of single oral dose of grape seed polyphenols restores blood pressure in a rat model of metabolic syndrome: role of nitric oxide and prostacyclin. Eur J Nutr 55, 749–758 (2016). https://doi.org/10.1007/s00394-015-0895-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-015-0895-0

Keywords

Search

Navigation