Inhibitors of 20-hydroxyeicosatetraenoic acid (20-HETE) formation attenuate the natriuretic effect of dopamine.

European Journal of Pharmacology
Maria M Federik FernandezSusana Nowicki

Abstract

Endogenous renal dopamine is a major physiological regulator of renal ion transport; however its intracellular signaling pathways are not thoroughly understood. The present study examined the role of 20-hydroxyeicosatetraenoic acid (20-HETE), the major cytochrome P450 (CYP4A) metabolite of arachidonic acid formed in the renal cortex, on the natriuretic response to dopamine in Sprague Dawley rats. Infusion of dopamine (1.5μg/kg/min, i.v.) increased urine flow (1.9 fold over basal), sodium excretion (UNaV, 2.7 fold), fractional sodium excretion (FENa, 3.3 fold) and proximal and distal delivery of sodium by 1.5- and 2-fold respectively. Administration of two inhibitors of the synthesis of 20-HETE, 1-aminobenzotriazole (ABT) and N-hydroxy-N'-(-4-butyl-2-methylphenyl)formamidine (HET0016) reduced the response to dopamine by 65%. Induction of the renal expression of CYP4A enzymes with clofibrate did not alter the response to dopamine. The natriuretic response to dopamine was lower in Dahl salt-sensitive rats in comparison to an SS.BN5 consomic strain in which transfer of chromosome 5 from Brown Norway to Dahl salt-sensitive rats upregulates the renal expression of CYP4A protein and the production of 20-HETE. Treatment with HET0016 bl...Continue Reading

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Citations

Nov 27, 2014·Current Opinion in Nephrology and Hypertension·Fan FanRichard J Roman
May 1, 2015·American Journal of Physiology. Renal Physiology·Luis A Di CianoFernando R Ibarra
Jan 17, 2015·Current Opinion in Nephrology and Hypertension·Ming-Zhi Zhang, Raymond C Harris
Oct 25, 2013·American Journal of Physiology. Renal Physiology·Ming-Zhi ZhangRaymond C Harris

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