Faculty Collaboration Database

Cytochrome P-450-dependent metabolism of arachidonic acid in the kidney of rats with diabetes insipidus. Am J Physiol Renal Physiol 2005 Dec;289(6):F1333-40

Date

07/15/2005

Pubmed ID

16014574

DOI

10.1152/ajprenal.00188.2005

Scopus ID

2-s2.0-27944466804 (requires institutional sign-in at Scopus site)   6 Citations

Abstract

This study compared the renal metabolism of arachidonic acid in Brattleboro (BB) (vasopressin deficient) and Long-Evans (LE) control rats and the effects of a cytochrome P-450 (CYP) inhibitor 1-aminobenzotriazole (ABT) on renal function in these animals. The production of 20-hydroxyeicosatetraenoic acid (20-HETE) by renal cortical and outer medullary microsomes was significantly greater in BB than in LE rats (155 +/- 16 vs. 92 +/- 13 and 59 +/- 7 vs. 33 +/- 3 pmol.min(-1).mg protein(-1)). Renal cortical epoxygenase activity was not different in these strains. The expression of CYP4A proteins was 58 and 78% higher in the renal cortex and outer medulla of BB than in LE rats. Chronic treatment of BB rats with a vasopressin type 2 receptor agonist for 1 wk normalized the renal production of 20-HETE. Chronic blockade of the formation of 20-HETE and EETs with ABT had little effect on renal function in LE rats. However, urine flow increased by 54% and urine osmolarity decreased by 33% in BB rats treated with ABT. Plasma levels of oxytocin fell significantly from 7.2 +/- 1.3 to 3.9 +/- 1.0 pg/ml. The effects of ABT in BB rats were attenuated by chronic infusion of oxytocin (0.7 ng.min(-1).100 g(-1)) to maintain fixed high plasma levels of this hormone. These results indicate that the expression of CYP4A protein and the renal formation of 20-HETE are elevated in the kidney of BB rats due to a lack of vasopressin and that chronic blockade of the formation of 20-HETE and EETs with ABT promotes water excretion in vasopressin-deficient BB rats by reducing the circulating levels of oxytocin, which is a weak vasopressin agonist.

Author List

Sarkis A, Ito O, Mori T, Kohzuki M, Ito S, Verbalis J, Cowley AW Jr, Roman RJ

Author

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

8,11,14-Eicosatrienoic Acid
Animals
Arachidonic Acid
Cytochrome P-450 CYP4A
Dehydration
Diabetes Insipidus
Hydroxyeicosatetraenoic Acids
Kidney
Male
Oxytocin
Rats
Rats, Inbred BB
Rats, Long-Evans
Triazoles