title: Hyperuricemia attenuates aortic nitric oxide generation, through inhibition of arginine transport, in rats.
abstract: OBJECTIVE
  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.affiliation: Department of Nephrology, Tel Aviv Sourasky Medical Center, Tel Aviv University, Sackler School of Medicine, Tel Aviv, Israel.
authors.forename: Idit F
authors.initials: IF
authors.lastname: Schwartz
authors.forename: Ayelet
authors.initials: A
authors.lastname: Grupper
authors.forename: Tamara
authors.initials: T
authors.lastname: Chernichovski
authors.forename: Avishai
authors.initials: A
authors.lastname: Grupper
authors.forename: Oren
authors.initials: O
authors.lastname: Hillel
authors.forename: Anat
authors.initials: A
authors.lastname: Engel
authors.forename: Doron
authors.initials: D
authors.lastname: Schwartz
mesh_terms: D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D001120:Arginine / Q000378:metabolism* / Q000494:pharmacology; D001553:Benzbromarone / Q000494:pharmacology; D001692:Biological Transport; D001794:Blood Pressure / Q000187:drug effects; D027201:Cationic Amino Acid Transporter 1 / Q000378:metabolism*; D004195:Disease Models, Animal; D033461:Hyperuricemia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010094:Oxonic Acid; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014527:Uric Acid / Q000097:blood; D014528:Uricosuric Agents / Q000494:pharmacology
chemical_list: D027201:Cationic Amino Acid Transporter 1; D014528:Uricosuric Agents; D014527:Uric Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D001553:Benzbromarone; D010094:Oxonic Acid; D000493:Allopurinol; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D051571:Protein Kinase C-alpha