Effects of eprosartan on mitochondrial membrane potential and H2O2 levels in leucocytes in hypertension.
We investigated whether circulating leucocytes from hypertensive patients exhibit more spontaneous, stimulated hydrogen peroxide (H2O2) production and greater mitochondrial membrane potential (Deltapsi) than those from normotensive individuals. We also investigated the effects of oral treatment with the angiotensin II (AT II) type 1 receptor blocker eprosartan (600 mg day(-1)) on these markers of oxidative stress. In 25 hypertensive patients and 28 healthy volunteers, spontaneous H2O2 formation was measured by flow cytometry after preincubation of buffy coat-leucocytes from fresh peripheral venous blood at 37 degrees C with 2',7' dichlorofluorescein. Stimulation of H2O2 formation by circulating leucocytes was elicited by the addition of tert-butylhydroperoxide (tBHP). Deltapsi was determined by flow cytometry after the addition of tetramethylrhodamine methyl ester (TMRM). Compared with healthy individuals, lymphocytes from hypertensive patients exhibited higher Deltapsi (12.28+/-3.20 vs 16.25+/-2.88 arbitrary fluorescence units (AFU), respectively; P<0.001) and greater spontaneous H2O2 production (4.75+/-5.15 vs 8.98+/-9.97 AFU, respectively; P<0.05). tBHP stimulation was associated with higher H2O2 levels in circulating leucocytes in patients with uncorrected hypertension than in normotensive individuals. H2O2 overproduction was corrected by eprosartan treatment. These results suggest that oxidative stress could be important in the pathogenesis of hypertension. Furthermore, measurement of leucocyte oxidant activities may be useful for the evaluation of oxidative stress, which may be reduced with the use of antihypertensive drugs. Our results demonstrate that treatment of hypertension with eprosartan normalizes blood pressure and corrects oxidative disturbances, suggesting that leucocytes could be a target for this drug.
Labiós
M
M
Hypertension Unit, Department of Internal Medicine, Valencia University Clinic Hospital, Valencia, Spain.
Martínez
M
M
Gabriel
F
F
Guiral
V
V
Ruiz-Aja
S
S
Beltrán
B
B
Muñoz
A
A
D000179:Acrylates / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D010865:Pilot Projects; D012235:Rhodamines / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology* / Q000627:therapeutic use; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D000179:Acrylates; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D007093:Imidazoles; D012235:Rhodamines; D013876:Thiophenes; C401833:tetramethylrhodamine methyl ester; C068373:eprosartan; D020122:tert-Butylhydroperoxide; D006861:Hydrogen Peroxide