Renal cytochrome P-450-related arachidonate metabolism in rabbit aortic coarctation.
Cells of the medullary segment of the thick ascending limb of Henle's loop (TALH) convert arachidonic acid (AA) via the cytochrome P-450 monooxygenase pathway to biologically active metabolites: P1, a vasorelaxant, and P2, an inhibitor of Na+-K+-ATPase activity. These AA metabolites may contribute to the renal vascular and metabolic adjustments in response to renal hypoperfusion and the attendant elevation of blood pressure produced by suprarenal aortic coarctation. On the eighth postoperative day, the blood pressures of hypertensive and sham-operated control rabbits were 105 (90-115) and 63 (60-64) mmHg (medians with semiquartile values), respectively (P less than 0.01). Formation of P1 and P2 was increased twofold in TALH cells obtained from hypertensive rabbits: 2.35 (1.79-4.83) and 1.28 (1.56-4.56) micrograms AA converted.mg protein-1.30 min-1 compared with sham-operated rabbits: 1.27 (1.03-1.53) and 0.64 (0.58-1.10) micrograms AA converted.mg protein-1.30 min-1 (P less than 0.05). The profile of biological activity of AA metabolites contained within P1 and P2 was unaffected by aortic coarctation. The cytochrome P-450 monooxygenase-derived AA metabolites may exert a defensive function to limit the degree of TALH cell injury in response to renal hypoperfusion and associated zonal anoxia by reducing energy-dependent Na+-K+-ATPase activity and affecting local vasodilatation.
Carroll
M A
MA
Department of Pharmacology, New York Medical College, Valhalla 10595.
Schwartzman
M
M
Baba
M
M
Miller
M J
MJ
McGiff
J C
JC
D000818:Animals; D001017:Aortic Coarctation / Q000201:enzymology*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001784:Blood Gas Analysis; D001794:Blood Pressure; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006973:Hypertension / Q000201:enzymology; D007668:Kidney / Q000098:blood supply / Q000201:enzymology*; D008297:Male; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D001095:Arachidonic Acids; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D000254:Sodium-Potassium-Exchanging ATPase