| Indoleamine 2,3-diooxygenase in periaortic fat: mechanisms of inhibition of contraction. | |
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MedLine Citation:
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PMID: 21841011 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Indoleamine 2,3-dioxygenase (IDO) metabolizes L-tryptophan to L-kynurenine, promotes immunosuppression and has been described as a consumer of superoxide. We discovered IDO expression in periaortic fat and tested the hypothesis that periarterial IDO functionally reduces agonist-induced contraction. Our model was the thoracic aorta, abdominal aorta and superior mesenteric artery of the male Sprague-Dawley rat. Periaortic fat from thoracic aorta stained intensely for IDO, the brown fat marker uncoupling protein -1 (UCP-1) and Oil Red O as a general lipid marker. White fat around the mesenteric artery and abdominal aorta stained less for IDO; brown fat was less abundant. IDO activity (kynurenine/tryptophan ratio via HPLC) was detected in visceral and mesenteric artery fat (ratio = ~4) but was highest in perithoracic aortic fat (ratio = 10±1.1). In isometric contractile experiments, periadventitial fat reduced angiotensin II-induced thoracic aortic (+ fat = 34% of -fat) and mesenteric artery (63% of -fat) maximal contraction. By contrast, periadventitial fat did not reduce agonist-induced contraction in abdominal aorta. The IDO inhibitor 1-L-methyltryptophan (1-MT) reversed the fat-induced reduction of angiotensin II-induced contraction in thoracic aorta but not mesenteric artery. The IDO metabolite kynurenine relaxed thoracic aorta only at high (9 mM) concentrations while the downstream metabolite quinolinic acid (1 mM) relaxed contracted thoracic aorta (~80%). 1-MT did not correct the reduction in basal superoxide levels observed in the presence of peri thoracic aortic fat. We conclude that IDO is an enzyme active primarily in brown fat surrounding the thoracic aorta and depresses aortic contractility. |
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Authors:
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Stephanie W Watts; Samantha Shaw; Robert Burnett; Anne M Dorrance |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-12 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: - ISSN: 1522-1539 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Michigan State University. |
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