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Am J Physiol Regul Integr Comp Physiol. 2004 Jul;287(1):R58-68. Epub 2004 Mar 18.

Inhibition of the formation of EETs and 20-HETE with 1-aminobenzotriazole attenuates pressure natriuresis.

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1
Medical College of Wisconsin, Dept. of Physiology, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.

Abstract

This study examined the effects of chronic blockade of the renal formation of epoxyeicosatrienoic acids and 20-hydroxyeicosatetraenoic acid with 1-aminobenzotriazole (ABT; 50 mg.kg(-1). day(-1) ip for 5 days) on pressure natriuresis and the inhibitory effects of elevations in renal perfusion pressure (RPP) on Na(+)-K(+)-ATPase activity and the distribution of the sodium/hydrogen exchanger (NHE)-3 in the proximal tubule of rats. In control rats (n = 15), sodium excretion rose from 2.3 +/- 0.4 to 19.4 +/- 1.8 microeq.min(-1).g kidney weight(-1) when RPP was increased from 114 +/- 1 to 156 +/- 2 mmHg. Fractional excretion of lithium rose from 28 +/- 3 to 43 +/- 3% of the filtered load. Chronic treatment of the rats with ABT for 5 days (n = 8) blunted the natriuretic response to elevations in RPP by 75% and attenuated the increase in fractional excretion of lithium by 45%. In vehicle-treated rats, renal Na(+)-K(+)-ATPase activity fell from 31 +/- 5 to 19 +/- 2 micromol P(i).mg protein(-1).h(-1) and NHE-3 protein was internalized from the brush border of the proximal tubule after an elevation in RPP. In contrast, Na(+)-K(+)-ATPase activity and the distribution of NHE-3 protein remained unaltered in rats treated with ABT. These results suggest that cytochrome P-450 metabolites of arachidonic acid contribute to pressure natriuresis by inhibiting Na(+)-K(+)-ATPase activity and promoting internalization of NHE-3 protein from the brush border of the proximal tubule.

PMID:
15031141
DOI:
10.1152/ajpregu.00713.2003
[Indexed for MEDLINE]
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