AJP - Regulatory, Integrative and Comparative Physiology, Vol 267, Issue 2 579-R589, Copyright © 1994 by American Physiological Society
Altered renal P-450 metabolism of arachidonic acid in Dahl salt-sensitive rats
Y. H. Ma, M. L. Schwartzman and R. J. Roman
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
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.
