title: Time-dependent increases in ouabain-sensitive Na+, K+ -ATPase activity in aortas from diabetic rats: The role of prostanoids and protein kinase C.
abstract: OBJECTIVE
  Na(+), K(+)-ATPase activity contributes to the regulation of vascular contractility and it has been suggested that vascular Na(+), K(+)-ATPase activity may be altered during the progression of diabetes; however the mechanisms involved in the altered Na(+), K(+)-ATPase activity changes remain unclear. Thus, the aim of the present study was to evaluate ouabain-sensitive Na(+), K(+)-ATPase activity and the mechanism(s) responsible for any alterations on this activity in aortas from 1- and 4-week streptozotocin-pretreated (50 mg kg(-1), i.v.) rats.
  
  
  METHODS
  Aortic rings were used to evaluate the relaxation induced by KCl (1-10mM) in the presence and absence of ouabain (0.1 mmol/L) as an index of ouabain-sensitive Na(+), K(+)-ATPase activity. Protein expression of COX-2 and p-PKC-betaII in aortas were also investigated.
  
  
  RESULTS
  Ouabain-sensitive Na(+), K(+)-ATPase activity was unaltered following 1-week of streptozotocin administration, but was increased in the 4-week diabetic aorta (27%). Endothelium removal or nitric oxide synthase inhibition with l-NAME decreased ouabain-sensitive Na(+), K(+)-ATPase activity only in control aortas. In denuded aortic rings, indomethacin, NS-398, ridogrel or Gö-6976 normalized ouabain-sensitive Na(+), K(+)-ATPase activity in 4-week diabetic rats. In addition, COX-2 (51%) and p-PKC-betaII (59%) protein expression were increased in 4-week diabetic aortas compared to controls.
  
  
  CONCLUSIONS
  In conclusion, diabetes led to a time-dependent increase in ouabain-sensitive Na(+), K(+)-ATPase activity. The main mechanism involved in this activation is the release of TxA(2)/PGH(2) by COX-2 in smooth muscle cells, linked to activation of the PKC pathway.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Luana C
authors.initials: LC
authors.lastname: Gallo
authors.forename: Ana Paula C
authors.initials: AP
authors.lastname: Davel
authors.forename: Fabiano E
authors.initials: FE
authors.lastname: Xavier
authors.forename: Luciana V
authors.initials: LV
authors.lastname: Rossoni
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D010042:Ouabain / Q000494:pharmacology*; D044262:Prostaglandin H2 / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013928:Thromboxane A2 / Q000378:metabolism; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D011453:Prostaglandins; D044262:Prostaglandin H2; D013928:Thromboxane A2; D010042:Ouabain; D051546:Cyclooxygenase 2; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase