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 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.
Dos Santos
Elisabete A
EA
Medical College of Wisconsin, Dept. of Physiology, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA.
Dahly-Vernon
Annette J
AJ
Hoagland
Kimberly M
KM
Roman
Richard J
RJ
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D002499:Centrifugation, Density Gradient; D065607:Cytochrome P-450 Enzyme Inhibitors; D015777:Eicosanoids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006893:Hydroxyeicosatetraenoic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology*
D065607:Cytochrome P-450 Enzyme Inhibitors; D015777:Eicosanoids; D004791:Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D014230:Triazoles; C033020:1-aminobenzotriazole; D016718:Arachidonic Acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D000254:Sodium-Potassium-Exchanging ATPase