AJP - Renal  AJP: Regulatory, Integrative and Comparative Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 QUICK SEARCH:   [advanced]


     


Am J Physiol Renal Physiol (July 12, 2005). doi:10.1152/ajprenal.00188.2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
289/6/F1333    most recent
00188.2005v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sarkis, A.
Right arrow Articles by Roman, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sarkis, A.
Right arrow Articles by Roman, R. J.
Submitted on May 5, 2005
Accepted on July 5, 2005

Cytochrome P450 dependent metabolism of arachidonic acid in the kidney of rats with diabetes insipidus

Albert Sarkis1, Osamu Ito2, Takefumi Mori3, Masahiro Kohzuki2, Sadayoshi Ito4, Joseph Verbalis5, Allen W. Cowley, Jr.1, and Richard J. Roman1*

1 Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA
2 Department of Internal Medicine and Rehabilitation Science, Tohoku University, Sendai, Japan
3 Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA; Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University, Sendai, Japan
4 Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University, Sendai, Japan
5 Department of Medicine, Georgetown University, Washington DC, USA

* To whom correspondence should be addressed. E-mail: rroman{at}mcw.edu.

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 P450 (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/mg protein). 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 one week normalized the renal production of 20-HETE. Chronic blockade of the formation of 20-HETE and EETs with ABT had little effects 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 infusing of oxytocin (0.7ng/min/100g) 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.







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.