title: The roles of intrarenal 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids in the regulation of renal function in hypertensive Ren-2 transgenic rats.
abstract: BACKGROUND
  The present study was performed in hypertensive Ren-2 transgenic rats (TGR) and in normotensive Hannover Sprague-Dawley (HanSD) rats. First, the intrarenal protein expression of CYP4A, the enzyme catalyzing the formation of 20-hydroxyeicosatetraenoic acid (20-HETE), and of CYP2C23, the enzyme responsible for epoxyeicosatrienoic acid (EET) production, was evaluated. Second, the renal functional responses to inhibition of the intrarenal formation of 20-HETE and EETs were investigated.
  
  
  METHODS
  Renal hemodynamics and electrolyte excretion were evaluated in response to the administration of inhibitors of 20-HETE and EET formation into the renal artery. In renal cortical tissue, CYP4A and CYP2C23 protein expression was assessed by Western blot analysis. Urinary concentrations of 20-HETE and EETs were measured using a fluorescent HPLC assay.
  
  
  RESULTS
  TGR have higher kidney CYP4A protein expression and urinary 20-HETE excretion but significantly lower CYP2C23 protein expression and urinary EET excretion than HanSD. Intrarenal inhibition of 20-HETE and EET formation decreased sodium excretion in HanSD, whereas inhibition of 20-HETE increased urinary excretion of sodium in TGR without altering renal hemodynamics.
  
  
  CONCLUSIONS
  Our data suggest that in TGR, deficient intrarenal synthesis of EETs combined with increased synthesis of 20-HETE with its stimulation of tubular sodium absorption may contribute to the development of hypertension in TGR.
authors.affiliation: Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Vera
authors.initials: V
authors.lastname: Certíková Chábová
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Kramer
authors.forename: Ivana
authors.initials: I
authors.lastname: Vanecková
authors.forename: Monika
authors.initials: M
authors.lastname: Thumová
authors.forename: Petra
authors.initials: P
authors.lastname: Skaroupková
authors.forename: Vladimír
authors.initials: V
authors.lastname: Tesar
authors.forename: John R
authors.initials: JR
authors.lastname: Falck
authors.forename: John D
authors.initials: JD
authors.lastname: Imig
authors.forename: Ludek
authors.initials: L
authors.lastname: Cervenka
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001095:Arachidonic Acids / Q000502:physiology*; D001794:Blood Pressure / Q000235:genetics; D006893:Hydroxyeicosatetraenoic Acids / Q000502:physiology*; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D007668:Kidney / Q000502:physiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley