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Induction of renal arachidonate cytochrome P-450 epoxygenase after uninephrectomy: counterregulation of hyperfiltration.

Takahashi K, Harris RC, Capdevila JH, Karara A, Makita K, Jacobson HR, Munger KA, Badr KF
J Am Soc Nephrol. 1993 3 (8): 1496-500

PMID: 8387830

After unilateral nephrectomy (UNx) in the rat, cytochrome P-450 (cP-450)-linked arachidonate enzymatic activity was markedly and specifically induced in microsomal fractions from the remaining kidney. The enzymatic activity reached 200% at 1 wk and 285% at 2 wk post-UNx as compared with non-UNx controls. Mean baseline values for GFR and RPF rate in the remaining kidney 2 wk after UNx were 1.56 +/- 0.10 and 6.47 +/- 0.35 mL/min, respectively. In these rats, the administration of ketoconazole, a cP-450 inhibitor, led to 75% inhibition of renal cP-450 arachidonate metabolism and was associated with acute augmentations in both GFR and RPF to 1.82 +/- 0.18 (P < 0.05 versus baseline) and 7.54 +/- 0.37 mL/min (P < 0.05 versus baseline), respectively. Because vasoconstrictor arachidonate epoxygenase products are endogenously generated in the rat kidney, these findings suggest that the stimulation of renal cP-450-mediated oxygenation of arachidonic acid may subserve an important counterregulatory function in mitigating the renal hyperperfusion and hyperfiltration that follow reductions in renal mass.

MeSH Terms (16)

Alkaline Phosphatase Animals Arachidonic Acid Cytochrome P-450 Enzyme Inhibitors Cytochrome P-450 Enzyme System Glomerular Filtration Rate Ketoconazole Kidney Male Microsomes Nephrectomy Oxygenases Rats Rats, Wistar Renal Circulation Sodium-Potassium-Exchanging ATPase

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