Effects of the angiotensin II type 1 receptor antagonist valsartan on the expression of superoxide dismutase in hypertensive patients

Hung Yu Yang, Pai Feng Kao, Tso Hsiao Chen, Brian Tomlinson, Wen Chin Ko, Paul Chan

研究成果: 雜誌貢獻文章

11 引文 斯高帕斯(Scopus)

摘要

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 super-oxide 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.

原文英語
頁(從 - 到)397-403
頁數7
期刊Journal of Clinical Pharmacology
47
發行號3
DOIs
出版狀態已發佈 - 三月 2007

    指紋

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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