| Differential effects of eNOS uncoupling on conduit and small arteries in GTP-cyclohydrolase I-deficient hph-1 mice. | |
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MedLine Citation:
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PMID: 21963838 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In the present study, we used the hph-1 mouse, which displays GTP-cyclohydrolase I (GTPCH I) deficiency, to test the hypothesis that loss of tetrahydrobiopterin (BH(4)) in conduit and small arteries activates compensatory mechanisms designed to protect vascular wall from oxidative stress induced by uncoupling of endothelial nitric oxide synthase (eNOS). Both GTPCH I activity and BH(4) levels were reduced in the aortas and small mesenteric arteries of hph-1 mice. However, the BH(4)-to-7,8-dihydrobiopterin ratio was significantly reduced only in hph-1 aortas. Furthermore, superoxide anion and 3-nitrotyrosine production were significantly enhanced in aortas but not in small mesenteric arteries of hph-1 mice. In contrast to the aorta, protein expression of copper- and zinc-containing superoxide dismutase (CuZnSOD) was significantly increased in small mesenteric arteries of hph-1 mice. Protein expression of catalase was increased in both aortas and small mesenteric arteries of hph-1 mice. Further analysis of endothelial nitric oxide synthase (eNOS)/cyclic guanosine monophosphate (cGMP) signaling demonstrated that protein expression of phosphorylated Ser(1177)-eNOS as well as basal cGMP levels and hydrogen peroxide was increased in hph-1 aortas. Increased production of hydrogen peroxide in hph-1 mice aortas appears to be the most likely mechanism responsible for phosphorylation of eNOS and elevation of cGMP. In contrast, upregulation of CuZnSOD and catalase in resistance arteries is sufficient to protect vascular tissue from increased production of reactive oxygen species generated by uncoupling of eNOS. The results of our study suggest that anatomical origin determines the ability of vessel wall to cope with oxidative stress induced by uncoupling of eNOS. |
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Authors:
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Livius V d'Uscio; Leslie A Smith; Zvonimir S Katusic |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2011-09-30 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 301 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-06 Completed Date: 2012-01-23 Revised Date: 2013-05-23 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H2227-34 Citation Subset: IM |
Affiliation:
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Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antioxidants / metabolism Aorta / enzymology* Biopterin / analogs & derivatives*, deficiency, metabolism Catalase / metabolism Cyclic GMP / metabolism GTP Cyclohydrolase / deficiency*, genetics Hydrogen Peroxide / metabolism Male Mesenteric Arteries / enzymology* Mice Mice, Inbred C57BL Mice, Knockout Nitric Oxide Synthase Type III / metabolism* Oxidative Stress Phosphorylation Serine Superoxide Dismutase / metabolism Superoxides / metabolism Tyrosine / analogs & derivatives, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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HL-53524/HL/NHLBI NIH HHS; HL-91867/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 11062-77-4/Superoxides; 17528-72-2/5,6,7,8-tetrahydrobiopterin; 22150-76-1/Biopterin; 3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine; 56-45-1/Serine; 6779-87-9/7,8-dihydrobiopterin; 7665-99-8/Cyclic GMP; 7722-84-1/Hydrogen Peroxide; EC 1.11.1.6/Catalase; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, mouse; EC 1.15.1.1/Superoxide Dismutase; EC 3.5.4.16/GTP Cyclohydrolase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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