Altered renal P-450 metabolism of arachidonic acid in Dahl salt-sensitive rats.

Abstract

The renal metabolism of arachidonic acid (AA) was compared in male and female prehypertensive Dahl salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats maintained on a low- (0.3%) sodium chloride diet. Renal cortical microsomes incubated with AA produced 20-hydroxyeicosatetraenoic acid (20-HETE), 14,15- and 11,12-epoxyeicosatrienoic acids, and a new metabolite of AA, 11,12-epoxy-20-hydroxyeicosatrienoic acid. The production of 20-HETE was similar in cortical microsomes of female SS/Jr and SR/Jr rats maintained on a low-salt diet (72 +/- 5 vs. 66 +/- 3 pmol.min-1.mg protein-1); however, the formation of epoxygenase metabolites was significantly less in SS/Jr than in SR/Jr rats (45 +/- 2 vs. 70 +/- 3 pmol.min-1.mg protein-1). Outer medullary microsomes produced primarily 20-HETE, and the formation of this compound was significantly lower in SS/Jr than in SR/Jr female rats fed a low-salt diet (8 +/- 2 vs. 18 +/- 3 pmol.min-1.mg protein-1). Renal papillary microsomes produced prostaglandin E2 and F2 alpha, and the formation of these compounds was similar in female SS/Jr and SR/Jr rats fed a low-salt diet. Similar differences in the metabolism of AA by P-450 were observed in microsomes prepared from the renal cortex and outer medulla of male SS/Jr and SR/Jr rats. These results indicate that the renal metabolism of AA by P-450 is altered in prehypertensive Dahl SS/Jr rats; however, the functional significance of this system in resetting renal function and in the development of hypertension in this model remains to be established.