Document Detail

Augmented S-nitrosylation contributes to impaired relaxation in angiotensin II hypertensive mouse aorta: role of thioredoxin reductase.
MedLine Citation:
PMID:  22025239     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Vascular dysfunction, including reduced endothelium-dependent dilation, is a major characteristic of hypertension. We previously investigated that thioredoxin reductase (TrxR) inhibition impairs vasodilation via soluble guanylyl cyclase S-nitrosylation, but S-nitrosylation and TrxR function are not known in hypertension. We hypothesized that S-nitrosylation is associated with reduced vasodilation in hypertensive mice.
METHOD: Aortic rings from normotensive (sham) and angiotensin II (AngII)-induced hypertensive C57BL/6 mice were treated with a TrxR inhibitor, 1-chloro-2,4-dinitrobenzene (DNCB) for 30  min, and relaxation to acetylcholine (ACh) was measured in the rings following contraction with phenylephrine.
RESULTS: DCNB reduced relaxation to ACh compared with vehicle in sham aorta but not in AngII (sham-vehicle E(max) = 77 ± 2, sham-DNCB E(max) = 59 ± 4, P < 0.05). DNCB shifted the concentration-response relaxation to sodium nitroprusside (SNP) to the right in both sham and AngII aortic rings (sham-vehicle pD(2) = 8.8±0.1, sham-DNCB pD(2) = 8.4±0.1, *P < 0.05; AngII-vehicle pD(2) = 8.5±0.1, AngII-DNCB pD(2) = 8.3 ± 0.1, P < 0.05). As downstream signaling of nitric oxide, cyclic GMP level was reduced by DNCB during activation with SNP. The effect of DNCB to increase S-nitrosylation was confirmed by the biotin-switch method and western blot analysis, and total protein S-nitrosylation was increased in AngII aorta (1.5-fold) compared with sham. TrxR activity was inhibited in AngII aorta compared with sham.
CONCLUSION: We conclude that increased S-nitrosylation contributes to impaired relaxation in aorta from AngII-induced hypertensive mice. AngII treatment resulted in inactivation of TrxR and increased S-nitrosylation, indicating that TrxR and S-nitrosylation may provide a critical mechanism in hypertension associated with abnormal vascular reactivity.
Hyehun Choi; Kyan J Allahdadi; Rita C Tostes; R Clinton Webb
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of hypertension     Volume:  29     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-15     Completed Date:  2012-03-20     Revised Date:  2014-05-14    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  2359-68     Citation Subset:  IM    
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MeSH Terms
Acetylcholine / pharmacology
Angiotensin II / pharmacology
Aorta, Thoracic / drug effects,  metabolism*,  pathology
Cyclic GMP / metabolism
Cysteine / analogs & derivatives*,  pharmacology
Dinitrochlorobenzene / pharmacology
Disease Models, Animal
Enzyme Inhibitors / pharmacology
Hypertension / metabolism*,  pathology
Mice, Inbred C57BL
Muscle Relaxation / drug effects
Muscle, Smooth, Vascular / drug effects,  physiopathology
Nitric Oxide / metabolism*
Nitric Oxide Donors / pharmacology*
Phenylephrine / pharmacology
S-Nitrosothiols / pharmacology*
Thioredoxin-Disulfide Reductase / antagonists & inhibitors*
Vascular Resistance / drug effects
Vasoconstrictor Agents / pharmacology
Vasodilator Agents / pharmacology
Grant Support
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Nitric Oxide Donors; 0/S-Nitrosothiols; 0/Vasoconstrictor Agents; 0/Vasodilator Agents; 11128-99-7/Angiotensin II; 1WS297W6MV/Phenylephrine; 31C4KY9ESH/Nitric Oxide; 51209-75-7/S-nitrosocysteine; EC Reductase; GE3IBT7BMN/Dinitrochlorobenzene; H2D2X058MU/Cyclic GMP; K848JZ4886/Cysteine; N9YNS0M02X/Acetylcholine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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