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.
Original language | English (US) |
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Pages (from-to) | 335-346 |
Number of pages | 12 |
Journal | Kidney and Blood Pressure Research |
Volume | 30 |
Issue number | 5 |
DOIs | |
State | Published - Sep 2007 |
Keywords
- 20-Hydroxyeicosatetraenoic acid
- Cytochrome P-450
- Epoxyeicosatrienoic acid
- Glomerular filtration rate
- Hypertension
- Renal plasma flow
- Renin transgenic rats
- Renin-angiotensin system
- Sodium excretion
ASJC Scopus subject areas
- Nephrology
- Cardiology and Cardiovascular Medicine