Original ArticleThioredoxin Reductase Inhibition Reduces Relaxation By Increasing Oxidative Stress and S-Nitrosylation in Mouse AortaChoi, Hyehun PhD; Tostes, Rita C. PhD; Webb, R. Clinton PhDAuthor Information Department of Physiology, Georgia Health Sciences University, Augusta, GA. Reprints: Hyehun Choi, PhD, Department of Physiology, Georgia Health Sciences University, 1120 Fifteenth St, CA-3101, Augusta, GA 30912-3000 (e-mail: firstname.lastname@example.org). Supported by grants from the National Institutes of Health (R01HL071138 and R01DK083685). The authors report no conflicts of interest. Received March 1, 2011 Accepted July 12, 2011 Journal of Cardiovascular Pharmacology: November 2011 - Volume 58 - Issue 5 - p 522-527 doi: 10.1097/FJC.0b013e31822d80a5 Buy Metrics Abstract Oxidative stress is well known to lead to vascular dysfunction. Thioredoxin reductase (TrxR) catalyzes the reduction of oxidized thioredoxin. Reduced thioredoxin plays a role in cellular antioxidative defense and in decreasing S-nitrosylation. It is not known whether TrxR affects vascular reactivity. We hypothesized that TrxR inhibition decreases vascular relaxation via increased oxidative stress and S-nitrosylation. Aortic rings from C57BL/6 mice were treated with the TrxR inhibitor, 1-chloro-2,4-dinitrobenzene (DNCB), or auranofin for 30 minutes. Vascular relaxation to acetylcholine was measured in the rings contracted with phenylephrine. DNCB and auranofin reduced relaxation compared with vehicle (vehicle Emax = 71 ± 3%, DNCB Emax = 53 ± 3%; P < 0.05). The antioxidants, apocynin (nicotinamide adenine dinucleotide phosphate oxidase inhibitor), and tempol (superoxide dismutase mimetic) normalized impaired relaxation by DNCB in aorta (DNCB Emax = 53 ± 3%, DNCB + tempol Emax = 66 ± 3%; P < 0.05). In addition, DNCB reduced sodium nitroprusside–induced relaxation. DNCB increased soluble guanylyl cyclase (sGC) S-nitrosylation and decreased sGC activity. These data suggest that TrxR regulates vascular relaxation via antioxidant defense and sGC S-nitrosylation. TrxR may be an enzyme to approach for treatment of vascular dysfunction and arterial hypertension. © 2011 Lippincott Williams & Wilkins, Inc.