Citric Acid Metabolism in Resistant Hypertension : Underlying Mechanisms and Metabolic Prediction of Treatment Response

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dc.contributor.author Martín Lorenzo, Marta
dc.contributor.author Martínez, Paula J.
dc.contributor.author Baldan Martin, Montserrat
dc.contributor.author Ruiz Hurtado, Gema
dc.contributor.author Carlos Prado, Jose
dc.contributor.author Segura, Julián
dc.contributor.author Cuesta, Fernando de la
dc.contributor.author Barderas, María G.
dc.contributor.author Vivanco, Fernando
dc.contributor.author Ruilope Urioste, Luis Miguel
dc.contributor.author Álvarez Llamas, Gloria
dc.date.accessioned 2018-01-08T11:54:12Z
dc.date.available 2018-01-08T11:54:12Z
dc.date.issued 2017
dc.identifier.citation Martin-Lorenzo, M., Martinez, P. J., Baldan-Martin, M., Ruiz-Hurtado, G., Prado, J. C., Segura, J., ... & Alvarez-Llamas, G. (2017). Citric Acid Metabolism in Resistant Hypertension : Underlying Mechanisms and Metabolic Prediction of Treatment Response. Hypertension, 70(5), 1049-1056. DOI: 10.1161/HYPERTENSIONAHA.117.09819 spa
dc.identifier.issn 0194-911X
dc.identifier.issn 1524-4563
dc.identifier.uri http://hdl.handle.net/11268/6990
dc.description.abstract Resistant hypertension (RH) affects 9% to 12% of hypertensive adults. Prolonged exposure to suboptimal blood pressure control results in end-organ damage and cardiovascular risk. Spironolactone is the most effective drug for treatment, but not all patients respond and side effects are not negligible. Little is known on the mechanisms responsible for RH. We aimed to identify metabolic alterations in urine. In addition, a potential capacity of metabolites to predict response to spironolactone was investigated. Urine was collected from 29 patients with RH and from a group of 13 subjects with pseudo-RH. For patients, samples were collected before and after spironolactone administration and were classified in responders (n=19) and nonresponders (n=10). Nuclear magnetic resonance was applied to identify altered metabolites and pathways. Metabolites were confirmed by liquid chromatography-mass spectrometry. Citric acid cycle was the pathway most significantly altered (P<0.0001). Metabolic concentrations were quantified and ranged from ng/mL malate to mu g/mL citrate. Citrate and oxaloacetate increased in RH versus pseudoresistant. Together with a-ketoglutarate and malate, they were able to discriminate between responders and nonresponders, being the 4 metabolites increased in nonresponders. Combined as a prediction panel, they showed receiver operating characteristic curve with area under the curve of 0.96. We show that citric acid cycle and deregulation of reactive oxygen species homeostasis control continue its activation after hypertension was developed. A metabolic panel showing alteration before spironolactone treatment and predicting future response of patients is shown. These molecular indicators will contribute optimizing the rate of control of RH patients with spironolactone. spa
dc.description.sponsorship SIN FINANCIACIÓN spa
dc.language.iso eng spa
dc.title Citric Acid Metabolism in Resistant Hypertension : Underlying Mechanisms and Metabolic Prediction of Treatment Response spa
dc.type article spa
dc.description.impact 6.823 JCR (2017) Q1, 3/65 Peripheral Vascular Disease spa
dc.identifier.doi 10.1161/HYPERTENSIONAHA.117.09819
dc.rights.accessRights closedAccess spa
dc.subject.uem Ácido cítrico spa
dc.subject.uem Hipertensión spa
dc.subject.unesco Sistema cardiovascular spa
dc.description.filiation UEM spa
dc.peerreviewed Si spa

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