The roles of intrarenal 20-hydroxyeicosatetraenoic and epoxyeicosatrienoic acids in the regulation of renal function in hypertensive Ren-2 transgenic rats.
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.
Certíková Chábová
Vera
V
Center for Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Kramer
Herbert J
HJ
Vanecková
Ivana
I
Thumová
Monika
M
Skaroupková
Petra
P
Tesar
Vladimír
V
Falck
John R
JR
Imig
John D
JD
Cervenka
Ludek
L
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