The principal arachidonate product of rat preglomerular microvessels (PGMV), 20-HETE, is an essential component in key renal vascular mechanisms that govern renal blood flow (autoregulation) and glomerular filtration rate (tubuloglomerular feedback). Therefore, identifying and characterizing those factors that determine synthesis and activity of 20-HETE are key to understanding the control of renal function. The proposed studies are based primarily on two experimental preparations: rat isolated PGMV and pressurized renal arcuate-interlobular arteries that provide complementary data. A third preparation, interlobar and arcuate arteries will provide additional information on eicosanoid metabolism as affected by changes in oxygenase enzyme activity under various experimental conditions. The biochemical effects of vasoactive peptides on PGMV will be correlated with changes in reactivity of pressurized arteries to the peptide challenge. They postulate four major factors that modify either the synthesis or effects of 20-HETE: 1) NO decreases 20-HETE synthesis by inhibiting w hydroxylases. 2) COX metabolizes 20-HETE to prostaglandin analogs (20-OH-PG) that differ in their biological activity from 20-HETE. Further, analogs produced by COX-1 differ from those produced by COX-2. 3) EETs (11,12-EET?) that antagonize the vasoconstrictor response to 20-HETE. 4) AT2 mediates Ang II-induced increases in 20-HETE levels in PGMV. Perturbation of the above factors by high and low salt diets will be related to effects on synthesis and vascular actions of 20-HETE.
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