The roles of intrarenal 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids in the regulation of renal function in hypertensive Ren-2 transgenic rats. Kidney Blood Press Res 2007;30(5):335-46
Date
09/06/2007Pubmed ID
17785988DOI
10.1159/000107710Scopus ID
2-s2.0-34748856828 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
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.
Author List
Certíková Chábová V, Kramer HJ, Vanecková I, Thumová M, Skaroupková P, Tesar V, Falck JR, Imig JD, Cervenka LMESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Genetically Modified
Arachidonic Acids
Blood Pressure
Hydroxyeicosatetraenoic Acids
Hypertension
Kidney
Male
Rats
Rats, Sprague-Dawley
