|Augmented S-nitrosylation contributes to impaired relaxation in angiotensin II hypertensive mouse aorta: role of thioredoxin reductase.|
|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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|Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural|
|Title: Journal of hypertension Volume: 29 ISSN: 1473-5598 ISO Abbreviation: J. Hypertens. Publication Date: 2011 Dec|
|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|
|Languages: eng Pagination: 2359-68 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
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
|R01 DK083685/DK/NIDDK NIH HHS; R01 HL071138/HL/NHLBI NIH HHS; R01DK083685/DK/NIDDK NIH HHS; R01HL071138/HL/NHLBI NIH HHS|
|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 188.8.131.52/Thioredoxin-Disulfide Reductase; GE3IBT7BMN/Dinitrochlorobenzene; H2D2X058MU/Cyclic GMP; K848JZ4886/Cysteine; N9YNS0M02X/Acetylcholine|
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