| Augmented S-nitrosylation contributes to impaired relaxation in angiotensin II hypertensive mouse aorta: role of thioredoxin reductase. | |
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MedLine Citation:
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PMID: 22025239 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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 Emax = 77 ± 2, sham-DNCB Emax = 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 pD2 = 8.8±0.1, sham-DNCB pD2 = 8.4±0.1, *P < 0.05; AngII-vehicle pD2 = 8.5±0.1, AngII-DNCB pD2 = 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. |
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Authors:
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Hyehun Choi; Kyan J Allahdadi; Rita C Tostes; R Clinton Webb |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-10-21 |
Journal Detail:
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Title: Journal of hypertension Volume: - ISSN: 1473-5598 ISO Abbreviation: - Publication Date: 2011 Oct |
Date Detail:
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Created Date: 2011-10-25 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8306882 Medline TA: J Hypertens Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Physiology, Georgia Health Sciences University, Augusta, Georgia, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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