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Journal of the American Society of Nephrology, Vol 3, 1496-1500, Copyright © 1993 by American Society of Nephrology

REGULAR ARTICLES

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

K Takahashi, RC Harris, JH Capdevila, A Karara, K Makita, HR Jacobson, KA Munger and KF Badr
Department of Medicine, Vanderbilt University Medical School, Nashville, TN.

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.


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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
A. O. Oyekan, K. McAward, J. Conetta, L. Rosenfeld, and J. C. McGiff
Endothelin-1 and CYP450 arachidonate metabolites interact to promote tissue injury in DOCA-salt hypertension
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 1999; 276(3): R766 - R775.
[Abstract] [Full Text] [PDF]


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