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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 \u00b1 16 vs. 92 \u00b1 13 and 59 \u00b1 7 vs. 33 \u00b1 3 pmol\u00b7min<jats:sup>\u22121<\/jats:sup>\u00b7mg protein<jats:sup>\u22121<\/jats:sup>). 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 \u00b1 1.3 to 3.9 \u00b1 1.0 pg\/ml. The effects of ABT in BB rats were attenuated by chronic infusion of oxytocin (0.7 ng\u00b7min<jats:sup>\u22121<\/jats:sup>\u00b7100 g<jats:sup>\u22121<\/jats:sup>) 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.<\/jats:p>","DOI":"10.1152\/ajprenal.00188.2005","type":"journal-article","created":{"date-parts":[[2005,7,13]],"date-time":"2005-07-13T12:10:26Z","timestamp":1121256626000},"page":"F1333-F1340","source":"Crossref","is-referenced-by-count":7,"title":["Cytochrome<i>P<\/i>-450-dependent metabolism of arachidonic acid in the kidney of rats with diabetes 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