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2017 ; 12
(11
): e0187729
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Effects of four different antihypertensive drugs on plasma metabolomic profiles
in patients with essential hypertension
#MMPMID29121091
Hiltunen TP
; Rimpelä JM
; Mohney RP
; Stirdivant SM
; Kontula KK
PLoS One
2017[]; 12
(11
): e0187729
PMID29121091
show ga
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.