Effects of four different antihypertensive drugs on plasma metabolomic profiles in patients with essential hypertension
| Autor: | Robert P. Mohney, Timo P. Hiltunen, Jenni M. Rimpela, Kimmo Kontula, Steven M. Stirdivant |
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| Přispěvatelé: | Clinicum, Kimmo Kontula Research Group, Department of Medicine, University of Helsinki, HUS Internal Medicine and Rehabilitation |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Physiology GENOMIC ASSOCIATION ANALYSIS lcsh:Medicine Blood Pressure 030204 cardiovascular system & hematology Pharmacology Essential hypertension Vascular Medicine Biochemistry DISEASE ACYLCARNITINES 0302 clinical medicine Hydrochlorothiazide Drug Metabolism Blood plasma Medicine and Health Sciences Metabolites PREDICTORS Antihypertensive drug lcsh:Science Multidisciplinary Fatty Acids WIDE Drugs Middle Aged Lipids Body Fluids L-CARNITINE 3. Good health Treatment Outcome Blood Antihypertensive Drugs Losartan Bisoprolol Hypertension Female Essential Hypertension Anatomy Research Article medicine.drug Adult medicine.drug_class Blood Plasma 03 medical and health sciences Double-Blind Method BLOOD-PRESSURE RESPONSE HYDROCHLOROTHIAZIDE medicine Humans Metabolomics Pharmacokinetics Amlodipine CARDIOVASCULAR EVENTS Antihypertensive Agents business.industry lcsh:R Biology and Life Sciences medicine.disease Metabolism 030104 developmental biology Blood pressure 3121 General medicine internal medicine and other clinical medicine lcsh:Q LOSARTAN business Antihypertensives |
| Zdroj: | PLoS ONE, Vol 12, Iss 11, p e0187729 (2017) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Objective In order to search for metabolic biomarkers of antihypertensive drug responsiveness, we measured >600 biochemicals in plasma samples of subjects participating in the GENRES Study. Hypertensive men received in a double-blind rotational fashion amlodipine, bisoprolol, hydrochlorothiazide and losartan, each as a monotherapy for one month, with intervening one-month placebo cycles. Methods Metabolomic analysis was carried out using ultra high performance liquid chromatography-tandem mass spectrometry. Full metabolomic signatures (the drug cycles and the mean of the 3 placebo cycles) became available in 38 to 42 patients for each drug. Blood pressure was monitored by 24-h recordings. Results Amlodipine (P values down to 0.002), bisoprolol (P values down to 2 x 10−5) and losartan (P values down to 2 x 10−4) consistently decreased the circulating levels of long-chain acylcarnitines. Bisoprolol tended to decrease (P values down to 0.002) the levels of several medium- and long-chain fatty acids. Hydrochlorothiazide administration was associated with an increase of plasma uric acid level (P = 5 x 10-4) and urea cycle metabolites. Decreases of both systolic (P = 0.06) and diastolic (P = 0.04) blood pressure after amlodipine administration tended to associate with a decrease of plasma hexadecanedioate, a dicarboxylic fatty acid recently linked to blood pressure regulation. Conclusions Although this systematic metabolomics study failed to identify circulating metabolites convincingly predicting favorable antihypertensive response to four different drug classes, it provided accumulating evidence linking fatty acid metabolism to human hypertension. |
| Databáze: | OpenAIRE |
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