| Arginase Inhibition Restores in vivo Coronary Microvascular Function in Type 2 Diabetic Rats. | |
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MedLine Citation:
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PMID: 21297024 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aims - Nitric oxide (NO) is crucial for maintaining normal endothelial function and vascular integrity. Increased arginase activity in diabetes might compete with NO synthase (NOS) for their common substrate arginine resulting in diminished production of NO. The aim of the study was to evaluate coronary microvascular function in type 2 diabetic Goto Kakizaki (GK) rats using in vivo coronary flow velocity reserve (CFVR) and the effect of arginase inhibition to restore vascular function. Methods and Results - Different groups of GK and Wistar rats were given vehicle, the arginase inhibitor N(ω)-hydroxy-nor-L-arginine (nor-NOHA), L-arginine and the NOS inhibitor N(G)-monomethyl -L-arginine (L-NMMA). GK rats had impaired CFVR compared to Wistar rats (1.31±0.09 vs. 1.87±0.05; P<0.001). CFVR was restored by nor-NOHA treatment in comparison with vehicle in GK rats (1.71±0.13 vs. 1.23±0.12; P<0.05) but remained unchanged in Wistar rats (1.88±0.10 vs. 1.79±0.16). The beneficial effect of nor-NOHA in GK rats was abolished after NOS inhibition. CFVR was not affected by arginine in comparison with vehicle. Arginase II expression was increased in aorta and myocardium from GK rats compared to Wistar rats. The citrulline/ornithine and citrulline/arginine ratios measured in plasma increased significantly more in GK rats than in Wistar rats following nor-NOHA, suggesting a shift of arginine utilization from arginase to NOS. Conclusions - Coronary artery microvascular function is impaired in the type 2 diabetic GK rat. Treatment with nor-NOHA restores the microvascular function by a mechanism related to increased utilization of arginine by NOS and increased NO availability. |
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Authors:
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Julia Grönros; Christian Jung; Jon O Lundberg; Ruha Cerrato; Claes-Goran Ostenson; John Pernow |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-2-4 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: - ISSN: 1522-1539 ISO Abbreviation: - Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-2-7 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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1Karolinska Institute. |
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