Effects of the angiotensin II type 1 receptor antagonist valsartan on the expression of superoxide dismutase in hypertensive patients.
The role of oxidative stress in the pathogenesis of vascular diseases such as hypertension has been well recognized. Angiotensin (Ang) II is regarded as a pro-oxidant because it can stimulate the production of reactive oxygen species. The purpose of this study was to evaluate whether treatment with the Ang II type 1 (AT(1)) receptor antagonist valsartan has an antioxidant effect in patients with mild to moderate hypertension. A randomized, double-blind, placebo-controlled study was conducted in 48 stage I and II hypertensive subjects. Patients were followed every 4 weeks for 12 weeks after randomization to valsartan titrated to 80 to 160 mg once or twice daily or matching placebo. The erythrocyte superoxide dismutase (SOD) activity and expression of SOD-mRNA in polymorphonuclear leukocytes were measured before and after treatment. Valsartan showed concentration-dependent inhibition of reactive oxygen species generation in polymorphonuclear leukocytes from hypertensive patients. The erythrocyte superoxide dismutase activity before treatment was more than 2 times higher in hypertensive subjects compared to normal controls. Superoxide dismutase activity decreased significantly after 12 weeks of treatment with valsartan but did not change with placebo. The amount of SOD-mRNA in the polymorphonuclear leukocytes decreased progressively over 3 months in the hypertensive subjects receiving valsartan treatment but did not change in the placebo group. The production of reactive oxygen species is increased in hypertension, and superoxide dismutase activity is increased, presumably as a compensatory mechanism. Treatment with valsartan but not placebo resulted in a progressive down-regulation of SOD-mRNA expression and a reduction in superoxide dismutase activity, suggesting antioxidant activity and a reduction of reactive oxygen species generation. These findings imply that AT(1) receptor antagonists may provide benefits to hypertensive patients beyond blood pressure reduction.
Yang
Hung-Yu
HY
Division of Cardiology, Taipei Medical University-Wan Fang Hospital, No. 111 Hsing-Lung Road, Sec. 3, Wen-Shan District, Taipei City 116, Taiwan.
Kao
Pai-Feng
PF
Chen
Tso-Hsiao
TH
Tomlinson
Brian
B
Ko
Wen-Chin
WC
Chan
Paul
P
D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D015152:Blotting, Northern; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts / Q000706:statistics & numerical data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D013777:Tetrazoles / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D012333:RNA, Messenger; D013777:Tetrazoles; D000068756:Valsartan; D013482:Superoxide Dismutase; D014633:Valine