This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dandona, P. Articles by Garg, R. Search for Related Content PubMed PubMed Citation Articles by Dandona, P. Articles by Garg, R.

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

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 B (NF-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-B binding activity and the expression of total cellular p65, a protein component of NF-B, fell significantly (P < 0.01). The expression of inhibitor B (IB) increased significantly (P < 0.05). Plasma C-reactive protein (CRP) concentration fell significantly (P < 0.01). All indices, except IB, reverted toward baseline, 7 d after the cessation of the drug. IB persisted in an elevated state. Neither quinapril nor simvastatin given for 7 d produced a suppression of ROS generation, intranuclear NF-B, p65, or CRP, and these two agents did not alter cellular IB either. The untreated controls also did not demonstrate a change in their ROS generation or NF-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; IB, inhibitor B; MNC, mononuclear cell; NF-B, nuclear factor B; PMN, polymorphonuclear cell; ROS, reactive oxygen species.

This article has been cited by other articles:

				T. M. Paravicini and R. M. Touyz NADPH Oxidases, Reactive Oxygen Species, and Hypertension: Clinical implications and therapeutic possibilities Diabetes Care, February 1, 2008; 31(Supplement_2): S170 - S180. [Abstract] [Full Text] [PDF]

				A. Ceriello Possible Role of Oxidative Stress in the Pathogenesis of Hypertension Diabetes Care, February 1, 2008; 31(Supplement_2): S181 - S184. [Abstract] [Full Text] [PDF]

				E. Grossman Does Increased Oxidative Stress Cause Hypertension? Diabetes Care, February 1, 2008; 31(Supplement_2): S185 - S189. [Abstract] [Full Text] [PDF]

				P. Rao, Z. H. Huang, and T. Mazzone Angiotensin II Regulates Adipocyte Apolipoprotein E Expression J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4366 - 4372. [Abstract] [Full Text] [PDF]

				Y. C. Chan and P. S. Leung Angiotensin II Type 1 Receptor-Dependent Nuclear Factor-{kappa}B Activation-Mediated Proinflammatory Actions in a Rat Model of Obstructive Acute Pancreatitis J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 10 - 18. [Abstract] [Full Text] [PDF]

				A. M. Jonk, A. J. H. M. Houben, R. T. de Jongh, E. H. Serne, N. C. Schaper, and C. D. A. Stehouwer Microvascular Dysfunction in Obesity: A Potential Mechanism in the Pathogenesis of Obesity-Associated Insulin Resistance and Hypertension Physiology, August 1, 2007; 22(4): 252 - 260. [Abstract] [Full Text] [PDF]

				K. Arishiro, M. Hoshiga, N. Negoro, D. Jin, S. Takai, M. Miyazaki, T. Ishihara, and T. Hanafusa Angiotensin Receptor-1 Blocker Inhibits Atherosclerotic Changes and Endothelial Disruption of the Aortic Valve in Hypercholesterolemic Rabbits J. Am. Coll. Cardiol., April 3, 2007; 49(13): 1482 - 1489. [Abstract] [Full Text] [PDF]

				H. Yokoyama, N. Katakami, and Y. Yamasaki Recent Advances of Intervention to Inhibit Progression of Carotid Intima-Media Thickness in Patients With Type 2 Diabetes Mellitus Stroke, September 1, 2006; 37(9): 2420 - 2427. [Abstract] [Full Text] [PDF]

				P. M Ridker, E. Danielson, N. Rifai, R. J. Glynn, and for the Val-MARC Investigators Valsartan, Blood Pressure Reduction, and C-Reactive Protein: Primary Report of the Val-MARC Trial Hypertension, July 1, 2006; 48(1): 73 - 79. [Abstract] [Full Text] [PDF]

				A. Nakamura, K. Shikata, M. Hiramatsu, T. Nakatou, T. Kitamura, J. Wada, T. Itoshima, and H. Makino Serum Interleukin-18 Levels Are Associated With Nephropathy and Atherosclerosis in Japanese Patients With Type 2 Diabetes Diabetes Care, December 1, 2005; 28(12): 2890 - 2895. [Abstract] [Full Text] [PDF]

				S. Kimura, G.-X. Zhang, A. Nishiyama, T. Shokoji, L. Yao, Y.-Y. Fan, M. Rahman, T. Suzuki, H. Maeta, and Y. Abe Role of NAD(P)H Oxidase- and Mitochondria-Derived Reactive Oxygen Species in Cardioprotection of Ischemic Reperfusion Injury by Angiotensin II Hypertension, May 1, 2005; 45(5): 860 - 866. [Abstract] [Full Text] [PDF]

				E. M. Stuveling, S. J. L. Bakker, H. L. Hillege, P. E. de Jong, R. O. B. Gans, and D. de Zeeuw Biochemical risk markers: a novel area for better prediction of renal risk? Nephrol. Dial. Transplant., March 1, 2005; 20(3): 497 - 508. [Full Text] [PDF]

				L. Sironi, P. Gelosa, U. Guerrini, C. Banfi, V. Crippa, M. Brioschi, E. Gianazza, E. Nobili, A. Gianella, M. de Gasparo, et al. Anti-Inflammatory Effects of AT1 Receptor Blockade Provide End-Organ Protection in Stroke-Prone Rats Independently from Blood Pressure Fall J. Pharmacol. Exp. Ther., December 1, 2004; 311(3): 989 - 995. [Abstract] [Full Text] [PDF]

				D. Fliser, K. Buchholz, H. Haller, and for the EUropean Trial on Olmesartan and Pravastat Antiinflammatory Effects of Angiotensin II Subtype 1 Receptor Blockade in Hypertensive Patients With Microinflammation Circulation, August 31, 2004; 110(9): 1103 - 1107. [Abstract] [Full Text] [PDF]

				A. Ceriello, L. Quagliaro, L. Piconi, R. Assaloni, R. Da Ros, A. Maier, K. Esposito, and D. Giugliano Effect of Postprandial Hypertriglyceridemia and Hyperglycemia on Circulating Adhesion Molecules and Oxidative Stress Generation and the Possible Role of Simvastatin Treatment Diabetes, March 1, 2004; 53(3): 701 - 710. [Abstract] [Full Text] [PDF]