20-hydroxyeicosatetraenoic acid and renal function in Lyon hypertensive rats

To evaluate the contribution of cytochrome P450 (CYP450) metabolites of ara chidonic acid in the increased renal vascular resistance and blunted pressu re-natriuresis response exhibited by Lyon hypertensive (LH) rats, the effec ts of an intrarenal infusion of 17-octadecynoic acid (3 mu M), an inhibitor of the formation of epoxyeicosatrienoic and 20-hydroxyeicosatetraenoic aci ds, were compared in 8-week-old LH and low blood pressure (LL) control rats . 17-Octadecynoic acid failed to affect renal function in LL rats. In contr ast, it reduced renal vascular resistance and shifted the pressure-natriure sis relationship to lower pressures in LH rats. Blockade of thromboxane-end operoxide (TP) receptors with GR 32191B prevented the renal vasodilator res ponse to 17-octadecynoic acid but not its natriuretic action. Miconazole (1 mu M), an inhibitor of epoxygenase activity, had no effect on renal functi on in LH rats. These results indicate that CYP450 metabolites of arachidoni c acid, likely 20-hydroxyeicosatetraenoic acid, contribute to the resetting of the pressure-natriuresis relation in LH rats and that the renal vasocon strictor effects of 20-hydroxyeicosatetraenoic acid in LH rats may be relat ed to activation of TP receptors. (C) 1999 Elsevier Science B.V. All rights reserved.