Renal cytochrome P-450-arachidonic acid metabolism: localization and hormonal regulation in SHR.

Epoxygenase and omega- and omega-1-hydroxylases are the major cytochrome P-450-arachidonate (P-450-AA) metabolizing enzymes in renal tissues. We measured P-450-AA metabolism in single nephron segments and determined the tubular localization of this activity in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Formation of 20-hydroxyeicosatetraenoic acid (20-HETE), the product of AA omega-hydroxylase was specifically localized in the entire proximal tubules (S1, S2, and S3 segments), whereas formation of 19-HETE, the product of omega-1-hydroxylase and epoxyeicosatrienoic acids (EETs), products of AA epoxygenase, was demonstrable throughout the tubule. Although distribution patterns were similar in SHR and WKY, formation of 19- and 20-HETE in the proximal tubules was higher in SHR, whereas the formation of EETs was not different between the two strains. In the proximal tubules, angiotensin II (ANG II) significantly stimulated epoxygenase activity (EETs formation), whereas parathyroid hormone (PTH) and epidermal growth factor (EGF) had no effect on epoxygenase but significantly stimulated omega-hydroxylase activity (20-HETE formation). Because P-450-AA metabolites have a wide and contrasting spectrum of biological and renal effects, from vasodilation to vasoconstriction and from inhibition to stimulation of Na(+)-K(+)-adenosinetriphosphatase, their localization to the specific nephron segments and differential stimulation of their formation by ANG II, PTH, and EGF may contribute not only to renal hemodynamics and blood pressure regulation but also to the regulation of renal sodium and water balance.