Inhibition of renin secretion from rat renal cortical slices by (R)-12-HETE.
The arachidonic acid metabolite 12-hydroxyeicosatetraenoic acid (12-HETE) inhibits renin secretion both in vivo and in vitro, but the enzymatic origin of the 12-HETE responsible for renin inhibition is unknown. These studies examined the effect of the 12-HETE stereoisomers (R)-12-HETE (a product of the cytochrome P-450 monooxygenase enzyme system) and (S)-12-HETE (a product of the lipoxygenase enzyme system) on basal and stimulated renin secretion from superficial cortical slices in the rat. First, rat cortex was shown to produce 12-HETE; chiral-phase high-performance liquid chromatography revealed that cortex produced 81% (S)-12-HETE and 19% (R)-12-HETE. (R)-12-HETE reduced basal renin release by 28 +/- 4% to 49 +/- 5% at concentrations of 10(-9) to 10(-7) M (P < 0.05 to 0.01). (S)-12-HETE did not significantly affect renin release. (R)-12-HETE also blunted isoproterenol-stimulated renin secretion (P < 0.05) at a concentration of 10(-6) M. 20-HETE, another cytochrome P-450 product, did not exert a significant effect on renin release. In summary, both (R)-12-HETE and (S)-12-HETE are synthesized by renal cortical tissue. Only (R)-12-HETE directly inhibits in vitro renin release. These findings suggest that the renal cytochrome P-450 enzyme system is capable of directly influencing local renin secretion.
Henrich
W L
WL
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
Falck
J R
JR
Campbell
W B
WB
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D001011:Aorta / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007672:Kidney Cortex / Q000378:metabolism*; D015289:Leukotrienes / Q000494:pharmacology; D008054:Lipid Peroxides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism*; D013237:Stereoisomerism; D000092502:Renin Inhibitors
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D016718:Arachidonic Acid; D006893:Hydroxyeicosatetraenoic Acids; D007545:Isoproterenol; D015289:Leukotrienes; D008054:Lipid Peroxides; D012083:Renin; D000092502:Renin Inhibitors; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid