12-lipoxygenase products are potent inhibitors of prostacyclin-induced renin release.
In isolated human or rat glomeruli, arachidonic acid can be metabolized by the cyclooxygenase pathway to prostaglandins or by the lipoxygenase pathway to hydroxyeicosatetraenoic acids (HETES). We have recently shown that 12-lipoxygenase products are potent inhibitors of renin release. Since prostacyclin (PGI2) is a potential renin secretagogue, we studied the direct effects of 12-lipoxygenase products on prostacyclin-induced renin secretion. Treatment of rat renal cortical slices with picomolar concentrations of 12-hydroperoxyeicosatetraenoic acid (12-HPETE) and 12-HETE blocked the prostacyclin- or iloprost (an analog of PGI2)-induced renin secretion. The inhibitory effects of 12-lipoxygenase products were not exhibited by the 5-lipoxygenase-derived products, leukotriene B4 and 5-HPETE. These results suggest that HETES are not only potent modulators of prostacyclin actions on renin, but that the concerted actions of these compounds in cells may be critical determinants of the juxtaglomerular cell secretion of renin.
Section of Endocrinology, USC Medical Center, Los Angeles 90033.
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D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology; D046508:Culture Techniques; D011464:Epoprostenol / Q000494:pharmacology*; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D016285:Iloprost; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D015289:Leukotrienes / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002317:Cardiovascular Agents; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D014662:Vasoconstrictor Agents; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C021201:12-HPETE; D011464:Epoprostenol; D008084:Lipoxygenase; D012083:Renin; D016285:Iloprost