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

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 mueq.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 mumol 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.