Abstract
Purpose
Serum nitric oxide (NO) reduction and increased endothelin-1 (ET-1) play a pivotal role in endothelial dysfunction and hypertension. Considering that traditional Mediterranean diet (TMD) reduces blood pressure (BP), the aim of this study was to analyze whether TMD induced changes on endothelial physiology elements such as NO, ET-1 and ET-1 receptors which are involved in BP control.
Methods
Non-smoking women with moderate hypertension were submitted for 1 year to interventions promoting adherence to the TMD, one supplemented with extra virgin olive oil (EVOO) and the other with nuts versus a control low-fat diet (30 participants/group). BP, NO, ET-1 and related gene expression as well as oxidative stress biomarkers were measured.
Results
Serum NO and systolic BP (SBP) or diastolic BP (DBP) were negatively associated at baseline, as well as between NO and ET-1. Our findings also showed a DBP reduction with both interventions. A negative correlation was observed between changes in NO metabolites concentration and SBP or DBP after the intervention with TMD + EVOO (p = 0.033 and p = 0.044, respectively). SBP reduction was related to an impairment of serum ET-1 concentrations after the intervention with TMD + nuts (p = 0.008). We also observed changes in eNOS, caveolin 2 and ET-1 receptors gene expression which are related to NO metabolites levels and BP.
Conclusions
The changes in NO and ET-1 as well as ET-1 receptors gene expression explain, at least partially, the effect of EVOO or nuts on lowering BP among hypertensive women.
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References
Jousilahti P, Toumilehto J, Vartiainen E, Korhonen HJ, Pitkäniemi J, Nissinen A, Puska P (1995) Importance of risk factor clustering in coronary heart disease mortality and incidence in eastern Finland. J Cardiovasc Risk 2:63–70
Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G (1987) Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 84:9265–9269
Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411–415
Furchgott RF, Zawadzki JV (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376
Griendling KK, Alexander RW (1997) Oxidative stress and cardiovascular disease. Circulation 96:3264–3265
Brunner H, Cockcroft JR, Deanfield J, Donald A, Ferranini E, Halcox J, Kiowski W, Lüscher TF, Mancia G, Natali A, Oliver JJ, Pessina AC, Rizzoni D, Rossi GP, Salvetti A, Spieker LE, Taddei S, Webb DJ (2005) Endothelial function and dysfunction. Part II: association with cardiovascular risk factors and diseases. A statement by the Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension. J Hypertens 23:233–246
Dhaun N, Goddard J, Kohan DE, Pollock DM, Schiffrin EL, Webb DJ (2008) Role of endothelin-1 in clinical hypertension: 20 years on. Hypertension 52:452–459
Epstein BJ, Anderson S (2009) Endothelin receptor antagonists as antihypertensives: the next frontier. Expert Rev Cardiovasc Ther 7:675–687
Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, Grassi G, Heagerty AM, Kjeldsen SE, Laurent S, Narkiewicz K, Ruilope L, Rynkiewicz A, Schmieder RE, Boudier HA, Zanchetti A, Vahanian A, Camm J, De Caterina R, Dean V, Dickstein K, Filippatos G, Funck-Brentano C, Hellemans I, Kristensen SD, McGregor K, Sechtem U, Silber S, Tendera M, Widimsky P, Zamorano JL, Erdine S, Kiowski W, Agabiti-Rosei E, Ambrosioni E, Lindholm LH, Viigimaa M, Adamopoulos S, Agabiti-Rosei E, Ambrosioni E, Bertomeu V, Clement D, Erdine S, Farsang C, Gaita D, Lip G, Mallion JM, Manolis AJ, Nilsson PM, O’Brien E, Ponikowski P, Redon J, Ruschitzka F, Tamargo J, van Zwieten P, Waeber B, Williams B (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). J Hypertens 25:1105–1187
Strazzullo P, Ferro-Luzzi A, Siani A, Scaccini C, Sette S, Catasta G, Mancini M (1986) Changing the Mediterranean diet: effects on blood pressure. J Hypertens 4:407–412
Casas-Agustench P, López-Uriarte P, Ros E, Bulló M, Salas-Salvadó J (2011) Nuts, hypertension and endothelial function. Nutr Metabol Cardiovasc Dis 21:S21–S33
Martínez-González MA, Corella D, Salas-Salvadó J, Ros E, Covas MI, Fiol M, Wärnberg J, Arós F, Ruíz-Gutiérrez V, Lamuela-Raventós RM, Lapetra J, Muñoz MA, Martínez JA, Sáez G, Serra-Majem L, Pintó X, Mitjavila MT, Tur JA, Portillo MP, Estruch R, PREDIMED Study Investigators (2012) Cohort profile: design and methods of the PREDIMED study. Int J Epidemiol 41:377–385
Estruch R, Martínez-González MA, Corella D, Salas-Salvadó J, Ruiz-Gutiérrez V, Covas MI, Fiol M, Gómez-Gracia E, López-Sabater MC, Vinyoles E, Arós F, Conde M, Lahoz C, Lapetra J, Sáez G, Ros E, PREDIMED Study Investigators (2006) Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med 145:1–11
Toledo E, Hu FB, Estruch R, Buil-Cosiales P, Corella D, Salas-Salvado J, Covas MI, Arós F, Gómez-Gracia E, Fiol M, Lapetra J, Serra-Majem L, Pinto X, Lamuela-Raventós RM, Saez G, Bulló M, Ruiz-Gutiérrez V, Ros E, Sorli JV, Martinez-Gonzalez MA (2013) Effect of the Mediterranean diet on blood pressure in the PREDIMED trial: results from a randomized controlled trial. BMC Med 11:207
Nigg CR, Burbank PM, Padula C, Dufresne R, Rossi JS, Velicer WF, Laforge RG, Prochaska JO (1999) Stages of change across ten health risk behaviors for older adults. Gerontologist 9:473–482
Fernández-Ballart JD, Piñol JL, Zazpe I, Corella D, Carrasco P, Toledo E, Perez-Bauer M, Martínez-González MA, Salas-Salvadó J, Martín-Moreno JM (2010) Relative validity of a semi-quantitative food-frequency questionnaire in an elderly Mediterranean population of Spain. Br J Nutr 103:1808–1816
Elosua R, Marrugat J, Molina L, Pons S, Pujol E (1994) Validation of the Minnesota Leisure Time Physical Activity Questionnaire in Spanish men. The MARATHOM Investigators. Am J Epidemiol 139:1197–1209
Cheng GW, Wu HL, Huang YL (2008) Simultaneous determination of malondialdehyde and ofloxacin in plasma using an isocratic high-performance liquid chromatography/fluorescence detection system. Anal Chim Acta 616:230–234
Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340:1111–1115
Perticone A, Ceravolo R, Pujia A, Ventura G, Iacopino S, Scozzafava A, Chello M, Mastroroberto P, Verdecchia P, Schillaci G (2001) Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation 104:191–196
Giannotti G, Doerries C, Mocharla PS, Mueller MF, Bahlmann FH, Horvàth T, Jiang H, Sorrentino SA, Steenken N, Manes C, Marzilli M, Rudolph KL, Lüscher TF, Drexler H, Landmesser U (2010) Impaired endothelial repair capacity of early endothelial progenitor cells in prehypertension: relation to endothelial dysfunction. Hypertension 55:1389–1397
Ghiadoni L, Versari D, Magagna A, Kardasz I, Plantinga Y, Giannarelli C, Taddei S, Salvetti A (2007) Ramipril dose-dependently increases nitric oxide availability in the radial artery of essential hypertension patients. J Hypertens 25:361–366
Stauffer BL, Westby CM, DeSouza CA (2008) Endothelin-1, aging and hypertension. Curr Opin Cardiol 23:350–355
Weil BR, Westby CM, Greiner JJ, Stauffer BL, DeSouza CA (2012) Elevated endothelin-1 vasoconstrictor tone in prehypertensive adults. Can J Cardiol 28:347–353
Kleinbongard P, Dejam A, Lauer T, Rassaf T, Schindler A, Picker O, Scheeren T, Gödecke 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
Kelm M (1999) Nitric oxide metabolism and breakdown. Biochim Biophys Acta 1411:273–289
Leung JW, Wong WT, Koon HW, Mo FM, Tam S, Huang Y, Vanhoutte PM, Chung SS, Chung SK (2011) Transgenic mice over-expressing ET-1 in the endothelial cells develop systemic hypertension with altered vascular reactivity. PLoS One 6:e26994
Edwards DL, Arora CP, Bui DT, Castro LC (1996) Long-term nitric oxide blockade in the pregnant rat: effects on blood pressure and plasma levels of endothelin-1. Am J Obstet Gynecol 175:484–488
Bourque SL, Davidge ST, Adams MA (2011) The interaction between endothelin-1 and nitric oxide in the vasculature: new perspectives. Am J Physiol Regul Integr Comp Physiol 300:R1288–R1295
Stamler R (1991) Implications of the INTERSALT Study. Hypertension 17:16–20
Estruch R, Ros E, Salas-Salvadó J, Covas MI, Corella D, Arós F, Gómez-Gracia E, Ruiz-Gutiérrez V, Fiol M, Lapetra J, Lamuela-Raventos RM, Serra-Majem L, Pintó X, Basora J, Muñoz MA, Sorlí JV, Martínez JA, Martínez-González MA (2013) Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 4:1279–1290
Medina-Remón A, Tresserra-Rimbau A, Pons A, Tur JA, Martorell M, Ros E, Buil-Cosiales P, Sacanella E, Covas MI, Corella D, Salas-Salvadó J, Gómez-Gracia E, Ruiz-Gutiérrez V, Ortega-Calvo M, García-Valdueza M, Arós F, Saez GT, Serra-Majem L, Pinto X, Vinyoles E, Estruch R, Lamuela-Raventos RM (2015) Effects of total dietary polyphenols on plasma nitric oxide and blood pressure in a high cardiovascular risk cohort. The PREDIMED randomized trial. Nutr Metab Cardiovasc Dis 25:60–67
Esposito K, Marfella R, Ciotola M, Di Palo C, Giugliano F, Giugliano G, D’Armiento M, D’Andrea F, Giugliano D (2004) Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA 292:1440–1446
Ros E, Nuñez I, Pérez-Heras A, Serra M, Gilabert R, Casals E, Deulofeu R (2004) A walnut diet improves endothelial function in hypercholesterolemic subjects: a randomized crossover trial. Circulation 109:1609–1614
Cortés B, Nuñez I, Cofán M, Gilabert R, Pérez-Heras A, Casals E, Deulofeu R, Ros E (2006) Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function. J Am Coll Cardiol 48:1666–1671
Konstantinidou V, Covas MI, Muñoz-Aguayo D, Khymenets O, de la Torre R, Saez G, Tormos Mdel C, Toledo E, Marti A, Ruiz-Gutiérrez V, Ruiz Mendez MV, Fito M (2010) In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: a randomized controlled trial. FASEB J 24:2546–2557
Fleming I (2010) Molecular mechanisms underlying the activation of eNOS. Pflugers Arch 459:793–806
Weber MA, Black H, Bakris G, Krum H, Linas S, Weiss R, Linseman JV, Wiens BL, Warren MS, Lindholm LH (2009) A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension: a randomized, double-blind, placebo-controlled trial. Lancet 374:1423–1431
Walter MF, Jacob RF, Jeffers B, Ghadanfar MM, Preston GM, Buch J, Mason RP (2004) Serum levels of thiobarbituric acid reactive substances predict cardiovascular events in patients with stable coronary artery disease. J Am Coll Cardiol 44:1996–2002
Mitjavila MT, Fandos M, Salas-Salvadó J, Covas MI, Borrego S, Estruch R, Lamuela-Raventós R, Corella D, Martínez-Gonzalez MA, Sánchez JM, Bulló M, Fitó M, Tormos C, Cerdá C, Casillas R, Moreno JJ, Iradi A, Zaragoza C, Chaves J, Sáez GT (2013) The Mediterranean diet improves the systemic lipid and DNA oxidative damage in metabolic syndrome individuals. A randomized, controlled, trial. Clin Nutr 32:172–178
Fitó M, Guxens M, Corella D, Sáez G, Estruch R, de la Torre R, Francés F, Cabezas C, López-Sabater Mdel C, Marrugat J, García-Arellano A, Arós F, Ruiz-Gutierrez V, Ros E, Salas-Salvadó J, Fiol M, Solá R, Covas MI, PREDIMED Study Investigators (2007) Effect of a traditional Mediterranean diet on lipoprotein oxidation: a randomized controlled trial. Arch Intern Med 167:1195–1203
Moreno-Luna R, Muñoz-Hernandez R, Miranda ML, Costa AF, Jimenez-Jimenez L, Vallejo-Vaz AJ, Muriana FJ, Villar J, Stiefel P (2012) Olive oil polyphenols decrease blood pressure and improve endothelial function in young women with mild hypertension. Am J Hypertens 25:1299–1304
Storniolo CE, Roselló-Catafau J, Pintó X, Mitjavila MT, Moreno JJ (2014) Polyphenol fraction of extra virgin olive oil protects against endothelial dysfunction induced by high glucose and free fatty acids through modulation of nitric oxide and endothelin-1. Redox Biol 2C:971–977
Perona JS, Martínez-González J, Sanchez-Domínguez JM, Badimon L, Ruiz-Gutierrez V (2004) The unsaponifiable fraction of virgin olive oil in chylomicrons from men improves the balance between vasoprotective and prothrombotic factors released by endothelial cells. J Nutr 134:3284–3289
Acknowledgments
The authors thank the participants in the PREDIMED study for their continued collaboration. The Fundación Patrimonio Comunal Olivarero, Hojiblanca SA (Málaga, Spain), California Walnut Commission (Sacramento, CA, USA), Borges SA (Reus, Spain) and Morella Nuts SA (Reus, Spain) donated the olive oil, walnuts, almonds and hazelnuts, respectively. We also thank the Scientific and Technical services of the University of Barcelona for malondialdehyde determinations. This study was supported by the Spanish Ministry of Health (FIS PI10/0082, G03/140, RD06/0045), Fondo Europeo de Desarrollo Regional, the Spanish Ministry of Science (BFU2007-61727/BFI) and the Generalitat de Catalunya (2009SGR00438).
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Storniolo, C.E., Casillas, R., Bulló, M. et al. A Mediterranean diet supplemented with extra virgin olive oil or nuts improves endothelial markers involved in blood pressure control in hypertensive women. Eur J Nutr 56, 89–97 (2017). https://doi.org/10.1007/s00394-015-1060-5
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DOI: https://doi.org/10.1007/s00394-015-1060-5