Novel renal arachidonate metabolites.
Cells of the thick ascending limb of the loop of Henle (TALH) metabolize arachidonic acid (AA) via the cytochrome P450 monooxygenase system to biologically active products that are resolved into two peaks, P1 and P2, on reverse-phase HPLC. Each peak contains materials that have characteristic biological activity. P1 contains a material that relaxes blood vessels and is structurally similar to a vasodilator, the 5,6 epoxyeicosatrienoic acid (EET). P2 contains a material that inhibits cardiac Na+-K+-ATPase, the major component of which has been identified as the 11,12 dihydroxyeicosatrienoic acid. In mTALH cells obtained from rabbits made hypertensive by aortic coarctation, there was a selective increase in P1 and P2 formation compared to other renomedullary cells. We have identified AA metabolites in bovine corneal epithelium with biological properties and chemical features similar to those of mTALH cells. 12(R)hydroxyeicosatetraenoic acid (12(R) HETE) a possible derivative of the 11,12-EET, is produced by the cornea and also has been shown to inhibit Na+-K+-ATPase activity. Renal microsomes obtained from spontaneously hypertensive rats (SHRs) also metabolize AA via a cytochrome P450 monooxygenase pathway to three principal biologically active metabolites that are formed in increased amounts during the developmental phase of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
Carroll
M A
MA
Department of Pharmacology, New York Medical College, Valhalla 10595.
Schwartzman
M
M
Sacerdoti
D
D
McGiff
J C
JC
D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001794:Blood Pressure; D055598:Chemical Phenomena; D002621:Chemistry; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D008138:Loop of Henle / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D001095:Arachidonic Acids; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; C040776:5,6-epoxy-8,11,14-eicosatrienoic acid; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D000254:Sodium-Potassium-Exchanging ATPase; D015126:8,11,14-Eicosatrienoic Acid