P-384: Renal vasoactive eicosanoids: Interactions between cytochrome P450 and cyclooxygenase metabolites during salt depletion

Preglomerular microvessels (PGMVs) occupy the key position in governing the renal circulation. Characterization of mediators/modulators of PGMVs vasomotion is, therefore, essential to defining renal vascular mechanisms. 20-hydroxyeicosatetraenoic acid (HETE), a potent vasoconstrictor, is the principal eicosanoid produced by PGMVs (arcuate and interlobar arteries) via cytochrome P450 (CYP) monooxygenases and is released by angiotensin II (AII) via stimulation of AT2 receptors that activate phospholipase C. 20-HETE is metabolized by cyclooxygenase (COX) producing prostaglandin (PG) analogs (e.g., 20- OH- PGs), having biological effects that differ from unmetabolized 20-HETE. As low salt (LS) intake increases AII generation and COX-2 expression, we examined 20-HETE synthesis in renal arteries (PGMVs and interlobular arteries) from male Sprague-Dawley rats fed either normal (NS; 0.4% NaCl) or LS (0.05% NaCl) diets for 10 days. With NS intake, 20-HETE was higher (P