Low Dietary Salt Regulates Renal Vascular 20-Hydroxyeicosatetraenoic Acid Levels.
20-hydroxyeicosatetraenoic (HETE), a prohypertensive cytochrome P450 (CYP)-derived arachidonic acid (AA) metabolite, is a principal eicosanoid of preglomerular microvessels. Vascular 20-HETE release is stimulated by angiotensin II (AII) and is subject to metabolism by cyclooxygenase (COX)-2. As dietary salt alters AII levels and COX-2 expression, we studied 20-HETE levels from microdissected arcuate and interlobular arteries and interlobar arteries obtained from male Sprague-Dawley rats fed a control (0.4% NaCl) or low salt diet (LS; 0.05% NaCl). In controls (n=6), metabolism of 14C-AA (7μM) in the presence of NADPH (1mM) and indomethacin (INDO; 10μM) to 20-HETE was higher (P<0.05) in arcuate and interlobular arteries compared to interlobar arteries (25.2 ± 3.6 ng vs. 15.3 ± 2.3 ng/mg protein/30 min, respectively) based on reverse-phase HPLC retention times and on-line radiodetection. No regional differences in epoxide formation were evident between arcuate and interlobular arteries compared to interlobar arteries (21.9 ± 3.6 ng vs. 19.6 ± 3.7 ng/mg protein/30 min, respectively). LS treatment, for 7 days, selectively increased 20-HETE levels in interlobar arteries (24.6 ± 3.9 ng/mg protein/30 min) and increased medullary CYP-4A expression. However, in the absence of INDO, 20-HETE levels in arcuate and interlobular arteries, but not interlobar arteries, were diminished by 90% with LS treatment; changes that corresponded with induced cortical COX-2 expression. Thus, 20-HETE levels vary segmentally within the renal microvasculature. LS intake induces medullary CYP-4A expression and interlobar artery 20-HETE formation. Presumably, the diminished 20-HETE levels in arcuate and interlobular arteries, in the absence of COX inhibition, were a result of increased cortical COX-2 expression serving as a metabolic pathway for 20-HETE; the vasoconstrictor 20-HETE being metabolized by COX-2 to vasodilator prostaglandin analogs. Increased 20-HETE levels may account for the adverse effects of COX inhibitors with salt depletion.