Thioredoxin reductase inhibition reduces relaxation by increasing oxidative Stress and S-nitrosylation in mouse aorta

Hyehun Choi, Rita C. Tostes, R Clinton Webb

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 E max = 71 ± 3%, DNCB E max = 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 E max = 53 ± 3%, DNCB + tempol E max = 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.

Original languageEnglish (US)
Pages (from-to)522-527
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Volume58
Issue number5
DOIs
StatePublished - Nov 1 2011

Fingerprint

Thioredoxin-Disulfide Reductase
Dinitrochlorobenzene
Aorta
Oxidative Stress
Blood Vessels
Auranofin
Thioredoxins
Thioredoxin Reductase 1
Antioxidants
Nitroprusside
Phenylephrine
NADP
Inbred C57BL Mouse
Acetylcholine
Superoxide Dismutase
Oxidoreductases
Hypertension

Keywords

  • reactive oxygen species
  • soluble guanylyl cyclase
  • vascular relaxation

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Thioredoxin reductase inhibition reduces relaxation by increasing oxidative Stress and S-nitrosylation in mouse aorta. / Choi, Hyehun; Tostes, Rita C.; Webb, R Clinton.

In: Journal of Cardiovascular Pharmacology, Vol. 58, No. 5, 01.11.2011, p. 522-527.

Research output: Contribution to journalArticle

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