Citric Acid Metabolism in Resistant Hypertension

• DOI: 10.1161/hypertensionaha.117.09819
• Publication Date: 2017-09-06T00:40:35Z
• Authors: Marta Martin-Lorenzo; Paula J. Martinez; Montserrat Baldan...; Gema Ruiz-Hurtado; Jose Carlos Prado; Julian Segura; Fernando de la Cu...; Maria G. Barderas; Fernando Vivanco; Luis Miguel Ruilope; Gloria Alvarez-Ll...
• Keywords: Ácido cítrico; Male; 0301 basic medicine; Drug-Related Side Effects and Adverse Reactions; Drug Resistance; 610; Spironolactone; Urinalysis; Citric Acid; 03 medical and health sciences; Predictive Value of Tests; Hipertensión; Humans; Antihypertensive Agents; Sistema cardiovascular; Aged; Middle Aged; Prognosis; 3. Good health; Spain; Hypertension; Ketoglutaric Acids; Female; Chromatography, Liquid

Resistant hypertension (RH) affects 9% to 12% of hypertensive adults. Prolonged exposure 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 side effects are negligible. Little known on mechanisms responsible RH. We aimed identify metabolic alterations urine. In addition, a potential capacity metabolites predict response spironolactone was investigated. Urine collected from 29 with RH group 13 subjects pseudo-RH. For patients, samples were before after administration classified responders (n=19) nonresponders (n=10). Nuclear magnetic resonance applied altered pathways. Metabolites confirmed by liquid chromatography-mass spectrometry. Citric acid cycle pathway significantly (P<0.0001). Metabolic concentrations quantified ranged ng/mL malate μg/mL citrate. Citrate oxaloacetate increased versus pseudoresistant. Together α-ketoglutarate malate, they able discriminate between nonresponders, being 4 nonresponders. Combined as prediction panel, showed receiver operating characteristiccurve area under curve 0.96. show that citric deregulation reactive oxygen species homeostasis continue its activation developed. A panel showing alteration treatment predicting future shown. These molecular indicators will contribute optimizing rate spironolactone.