TY - JOUR 
A1 - Martín Lorenzo, Marta
AU - Martínez, Paula J.
AU - Baldán Martín, Montserrat
AU - Ruiz Hurtado, Gema
AU - Carlos Prado, José
AU - Segura, Julián
AU - Cuesta, Fernando de la
AU - Barderas, María G.
AU - Vivanco, Fernando
AU - Ruilope Urioste, Luis Miguel
AU - Álvarez Llamas, Gloria
T1 - Citric Acid Metabolism in Resistant Hypertension : Underlying Mechanisms and Metabolic Prediction of Treatment Response
Y1 - 2017
SN - 0194-911X

UR - http://hdl.handle.net/11268/6990
AB - 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.
KW - Ácido cítrico
KW - Hipertensión
KW - Sistema cardiovascular
LA - eng
ER -