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The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 9 4496-4501
Copyright © 2003 by The Endocrine Society

COMMENT

Angiotensin II Receptor Blocker Valsartan Suppresses Reactive Oxygen Species Generation in Leukocytes, Nuclear Factor-{kappa}B, in Mononuclear Cells of Normal Subjects: Evidence of an Antiinflammatory Action

Paresh Dandona, Vikramjeet Kumar, Ahmad Aljada, Husam Ghanim, Tufail Syed, Debborah Hofmayer, Priya Mohanty, Devjit Tripathy and Rajesh Garg

Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, and Kaleida Health, Buffalo, New York 14209

Address all correspondence and requests for reprints to: Paresh Dandona, M.D., Ph.D., F.R.C.P., F.A.C.P., F.A.C.C., Diabetes-Endocrinology Center of Western New York, 3 Gates Circle, Buffalo, New York 14209. E-mail: pdandona{at}kaleidahealth.org.

In view of the pro-oxidant and proinflammatory effects of angiotensin II, we have tested the hypothesis that valsartan, an angiotensin receptor blocker, may exert a suppressive action on reactive oxygen species (ROS) generation, nuclear factor {kappa}B (NF-{kappa}B) in mononuclear cells. Four groups of eight normal subjects were given 1) 160 mg daily of valsartan, 2) 80 mg daily of simvastatin, 3) 40 mg quinapril, or 4) no treatment. Fasting blood samples were obtained before treatment and at d 1, 8, and 14 (7 d after the cessation of the drug). After valsartan, ROS generation by polymorphonuclear cells and mononuclear cells fell significantly by more than 40% (P < 0.01). NF-{kappa}B binding activity and the expression of total cellular p65, a protein component of NF-{kappa}B, fell significantly (P < 0.01). The expression of inhibitor {kappa}B (I{kappa}B) increased significantly (P < 0.05). Plasma C-reactive protein (CRP) concentration fell significantly (P < 0.01). All indices, except I{kappa}B, reverted toward baseline, 7 d after the cessation of the drug. I{kappa}B persisted in an elevated state. Neither quinapril nor simvastatin given for 7 d produced a suppression of ROS generation, intranuclear NF-{kappa}B, p65, or CRP, and these two agents did not alter cellular I{kappa}B either. The untreated controls also did not demonstrate a change in their ROS generation or NF-{kappa}B binding activity or plasma CRP concentration. We conclude that valsartan at a modest dose exerts a profound and rapid ROS and inflammation-suppressive effect that may be relevant to its potential beneficial effects in atherosclerosis, diabetes, and congestive cardiac failure. In contrast, quinapril and simvastatin produced no similar effect over the period of 1 wk. Our observations may also have implications to clinical situations in which a rapid antiinflammatory effect is required.

Abbreviations: ACE, Angiotensin converting enzyme; ARB, angiotensin receptor blocker; CRP, C-reactive protein; I{kappa}B, inhibitor {kappa}B; MNC, mononuclear cell; NF-{kappa}B, nuclear factor {kappa}B; PMN, polymorphonuclear cell; ROS, reactive oxygen species.




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