TY - JOUR
T1 - Thioredoxin reductase inhibition reduces relaxation by increasing oxidative Stress and S-nitrosylation in mouse aorta
AU - Choi, Hyehun
AU - Tostes, Rita C.
AU - Webb, R. Clinton
N1 - Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2011/11
Y1 - 2011/11
N2 - 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.
AB - 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.
KW - reactive oxygen species
KW - soluble guanylyl cyclase
KW - vascular relaxation
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U2 - 10.1097/FJC.0b013e31822d80a5
DO - 10.1097/FJC.0b013e31822d80a5
M3 - Article
C2 - 21795991
AN - SCOPUS:80955158726
SN - 0160-2446
VL - 58
SP - 522
EP - 527
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 5
ER -