Altered renal P-450 metabolism of arachidonic acid in Dahl salt-sensitive rats.
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.
Ma
Y H
YH
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
Schwartzman
M L
ML
Roman
R J
RJ
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004351:Drug Resistance; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced* / Q000235:genetics*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride
D006893:Hydroxyeicosatetraenoic Acids; D011453:Prostaglandins; D016718:Arachidonic Acid; D012965:Sodium Chloride; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D003577:Cytochrome P-450 Enzyme System; D015126:8,11,14-Eicosatrienoic Acid