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Hyperuricemia Attenuates Aortic Nitric Oxide Generation, through Inhibition of Arginine Transport, in Rats.
MedLine Citation:
PMID:  21099230     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Objectives: Hyperuricemia provokes endothelial dysfunction (ECD). Decreased endothelial nitric oxide synthase (eNOS) activity is an important source of ECD. Cationic amino acid transporter-1 (CAT-1) is the specific arginine transporter for eNOS. We hypothesize that hyperuricemia inhibits arginine uptake. Methods: Experiments were performed in freshly harvested aortas from untreated animals and rats fed with oxonic acid (hyperuricemia), and compared to hyperuricemic rats treated with either allopurinol, benzbromarone or arginine. Results: Arginine transport was significantly decreased in hyperuricemia. Benzbromarone and arginine prevented the decrease in arginine transport in hyperuricemic rats while allopurinol did not. Arginine transport was significantly decreased in control rats treated with allopurinol. Blood pressure response to acetylcholine was significantly attenuated in hyperuricemic rats, an effect which was prevented in all other experimental groups. L-NAME inhibitable cGMP response to carbamyl-choline was significantly decreased in hyperuricemic rats and this was completely prevented by both benzbromarone and arginine, while allopurinol partially prevented the aforementioned phenomenon. Hyperuricemia induced a significant increase in protein nitration that was prevented by benzbromarone, allopurinol, and arginine. Protein abundance of CAT-1, PKCα, and phosphorylated PKCα remained unchanged in all experimental groups. Conclusions: In hyperuricemia, the decrease in aortic eNOS activity is predominantly the result of attenuated arginine uptake.
Authors:
Idit F Schwartz; Ayelet Grupper; Tamara Chernichovski; Avishai Grupper; Oren Hillel; Anat Engel; Doron Schwartz
Publication Detail:
Type:  Journal Article     Date:  2010-11-23
Journal Detail:
Title:  Journal of vascular research     Volume:  48     ISSN:  1423-0135     ISO Abbreviation:  J. Vasc. Res.     Publication Date:  2011  
Date Detail:
Created Date:  2011-04-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9206092     Medline TA:  J Vasc Res     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  252-60     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 S. Karger AG, Basel.
Affiliation:
Department of Nephrology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel.
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