Inhibition of renin secretion from rat renal cortical slices by (R)-12-HETE. Am J Physiol 1992 Oct;263(4 Pt 2):F665-70
Date
10/01/1992Pubmed ID
1415738DOI
10.1152/ajprenal.1992.263.4.F665Scopus ID
2-s2.0-0026485525 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
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.
Author List
Henrich WL, Falck JR, Campbell WBAuthor
William B. Campbell PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
12-Hydroxy-5,8,10,14-eicosatetraenoic AcidAnimals
Aorta
Arachidonic Acid
Hydroxyeicosatetraenoic Acids
In Vitro Techniques
Isoproterenol
Kidney Cortex
Leukotrienes
Lipid Peroxides
Rats
Rats, Sprague-Dawley
Renin
Stereoisomerism
