Structural determinants of the renal vascular response to 20-hydroxyeicosatetraenoic acid (20-HETE)

20-HETE is an endogenously-formed vasoconstrictor that plays a role in tubuloglomerular feedback and autoregulation of renal blood flow. However, little is known about the mechanism of action of this compound or whether a receptor is involved. The present study compared the effects of 20-HETE and a series of synthetic analogues on vascular diameter of isolated perfused renal arterioles of the rat to determine the structural requirements to elevate vascular tone. Cumulative dose-response relationships to 5-, 12-. 15-, 19-, 20-, 21-HETEs, and a dimethyl derivative of 20-HETE were determined in renal interlobular arteries (100-150 μm) treated with indomethacin (5 μM), baicalein (0.5 μM), and 17-ODYA (20 μM) to block the endogenous production of arachidonic acid metabolites. 20-HETE (0.01 to 1 μM) reduced the diameter of these vessels in a concentration dependent manner by a maximum of 18±3% (n=6 vessels). 21-HETE and dimethyl 20-HETE had a similar effect and reduced vascular diameter by a maximum of 16±3% (n=5) and 15±2% (n=6). respectively. In contrast, 5-, 12-, 15-, or 19-HETE had no effect on vascular diameter. Moreover, pretreatment of the vessels with 5-, 15-or 19-HETE(1 μM) blocked the vasoconstrictor response to 20-HETE. These results suggest that the vasoconstrictor response to HETEs is dependent on the presence of a hydroxyl group on the 20 or 21 carbon while 5-, 15- and 19-HETE act as antagonists to the vasoconstrictor response to 20-HETE.