Published Online
on January 17, 2005

A more recent version of this article appeared on January 25, 2005

This Article Full Text (PDF) All Versions of this Article: 111/3/343    most recent 01.CIR.0000153272.48711.B9v1 Alert me when this article is cited Alert me if a correction is posted 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 Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sola, S. Articles by Khan, B. V. Search for Related Content PubMed PubMed Citation Articles by Sola, S. Articles by Khan, B. V. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Antioxidants Metabolic Syndrome Hazardous Substances DB PROSTAGLANDIN F2ALPHA Related Collections Lipids Obesity Other diabetes Clinical Studies Endothelium/vascular type/nitric oxide

Submitted on August 16, 2004
Revised on September 30, 2004
Accepted on October 13, 2004

Irbesartan and Lipoic Acid Improve Endothelial Function and Reduce Markers of Inflammation in the Metabolic Syndrome. Results of the Irbesartan and Lipoic Acid in Endothelial Dysfunction (ISLAND) Study

Srikanth Sola MD, Muhammad Q.S. Mir MD, Faiz A. Cheema MD, Nadya Khan-Merchant PhD, Rekha G. Menon MD, Sampath Parthasarathy PhD, and Bobby V. Khan MD, PhD^*

From the Division of Cardiology, Emory University School of Medicine, Atlanta, Ga.

^* To whom correspondence should be addressed. E-mail: bkhan{at}emory.edu.

Background--The metabolic syndrome is associated with increased angiotensin II activity, induction of a proinflammatory and oxidative state, and endothelial dysfunction. We evaluated the ability of irbesartan, an angiotensin receptor blocker, and lipoic acid, an antioxidant, to affect endothelial function and inflammation in patients with the metabolic syndrome.

Methods and Results--We randomized 58 subjects with the metabolic syndrome in a double-blinded manner to irbesartan 150 mg/d (n=14), lipoic acid 300 mg/d (n=15), both irbesartan and lipoic acid (n=15), or matching placebo (n=14) for 4 weeks. Endothelium-dependent and -independent flow-mediated vasodilation was determined under standard conditions. Plasma levels of interleukin-6, plasminogen activator-1, and 8-isoprostane were measured. After 4 weeks of therapy, endothelium-dependent flow-mediated vasodilation of the brachial artery was increased by 67%, 44%, and 75% in the irbesartan, lipoic acid, and irbesartan plus lipoic acid groups, respectively, compared with the placebo group. Treatment with irbesartan and/or lipoic acid was associated with statistically significant reductions in plasma levels of interleukin-6 and plasminogen activator-1. In addition, treatment with irbesartan or irbesartan plus lipoic acid decreased 8-isoprostane levels. No significant changes in blood pressure were noted in any of the study groups.

Conclusions--Administration of irbesartan and/or lipoic acid to patients with the metabolic syndrome improves endothelial function and reduces proinflammatory markers, factors that are implicated in the pathogenesis of atherosclerosis.

Key words: metabolic syndrome • endothelium • inflammation • angiotensin

This article has been cited by other articles:

				G. Montalescot, H. Drexler, R. Gallo, T. Pearson, M. Thoenes, and D. L. Bhatt Effect of irbesartan and enalapril in non-ST elevation acute coronary syndrome: results of the randomized, double-blind ARCHIPELAGO study Eur. Heart J., November 2, 2009; 30(22): 2733 - 2741. [Abstract] [Full Text] [PDF]

				S. Satofuka, A. Ichihara, N. Nagai, K. Noda, Y. Ozawa, A. Fukamizu, K. Tsubota, H. Itoh, Y. Oike, and S. Ishida (Pro)renin Receptor Promotes Choroidal Neovascularization by Activating Its Signal Transduction and Tissue Renin-Angiotensin System Am. J. Pathol., December 1, 2008; 173(6): 1911 - 1918. [Abstract] [Full Text] [PDF]

				O. Glushakova, T. Kosugi, C. Roncal, W. Mu, M. Heinig, P. Cirillo, L. G. Sanchez-Lozada, R. J. Johnson, and T. Nakagawa Fructose Induces the Inflammatory Molecule ICAM-1 in Endothelial Cells J. Am. Soc. Nephrol., September 1, 2008; 19(9): 1712 - 1720. [Abstract] [Full Text] [PDF]

				D. I. Diz Lewis K. Dahl Memorial Lecture: The Renin-Angiotensin System and Aging Hypertension, July 1, 2008; 52(1): 37 - 43. [Full Text] [PDF]

				W.-J. Zhang, K. E. Bird, T. S. McMillen, R. C. LeBoeuf, T. M. Hagen, and B. Frei Dietary {alpha}-Lipoic Acid Supplementation Inhibits Atherosclerotic Lesion Development in Apolipoprotein E Deficient and Apolipoprotein E/Low-Density Lipoprotein Receptor Deficient Mice Circulation, January 22, 2008; 117(3): 421 - 428. [Abstract] [Full Text] [PDF]

				Y. Ishida, T. Ohara, Y. Okuno, T. Ito, Y. Hirota, K. Furukawa, K. Sakaguchi, W. Ogawa, and M. Kasuga {alpha}-Lipoic Acid and Insulin Autoimmune Syndrome Diabetes Care, September 1, 2007; 30(9): 2240 - 2241. [Full Text] [PDF]

				S. Gilliam-Davis, V. S. Payne, S. O. Kasper, E. N. Tommasi, M. E. Robbins, and D. I. Diz Long-term AT1 receptor blockade improves metabolic function and provides renoprotection in Fischer-344 rats Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1327 - H1333. [Abstract] [Full Text] [PDF]

				W.-J. Zhang, H. Wei, T. Hagen, and B. Frei {alpha}-Lipoic acid attenuates LPS-induced inflammatory responses by activating the phosphoinositide 3-kinase/Akt signaling pathway PNAS, March 6, 2007; 104(10): 4077 - 4082. [Abstract] [Full Text] [PDF]

				J. M. Luther, J. V. Gainer, L. J. Murphey, C. Yu, D. E. Vaughan, J. D. Morrow, and N. J. Brown Angiotensin II Induces Interleukin-6 in Humans Through a Mineralocorticoid Receptor-Dependent Mechanism Hypertension, December 1, 2006; 48(6): 1050 - 1057. [Abstract] [Full Text] [PDF]

				D. Ziegler, A. Ametov, A. Barinov, P. J. Dyck, I. Gurieva, P. A. Low, U. Munzel, N. Yakhno, I. Raz, M. Novosadova, et al. Oral Treatment With {alpha}-Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy: The SYDNEY 2 trial. Diabetes Care, November 1, 2006; 29(11): 2365 - 2370. [Abstract] [Full Text] [PDF]

				T. Miyata and C. van Ypersele de Strihou Renoprotection of angiotensin receptor blockers: beyond blood pressure lowering Nephrol. Dial. Transplant., April 1, 2006; 21(4): 846 - 849. [Full Text] [PDF]

				I. Samudio, M. Konopleva, H. Pelicano, P. Huang, O. Frolova, W. Bornmann, Y. Ying, R. Evans, R. Contractor, and M. Andreeff A Novel Mechanism of Action of Methyl-2-cyano-3,12 Dioxoolean-1,9 Diene-28-oate: Direct Permeabilization of the Inner Mitochondrial Membrane to Inhibit Electron Transport and Induce Apoptosis Mol. Pharmacol., April 1, 2006; 69(4): 1182 - 1193. [Abstract] [Full Text] [PDF]

				A. Zuccollo, C. Shi, R. Mastroianni, K. A. Maitland-Toolan, R. M. Weisbrod, M. Zang, S. Xu, B. Jiang, J. M. Oliver-Krasinski, A. J. Cayatte, et al. The Thromboxane A2 Receptor Antagonist S18886 Prevents Enhanced Atherogenesis Caused by Diabetes Mellitus Circulation, November 8, 2005; 112(19): 3001 - 3008. [Abstract] [Full Text] [PDF]