title: 20-HETE agonists and antagonists in the renal circulation.
abstract: The present study examined the effects of a series of 20-hydroxyeicosatetraenoic acid (20-HETE) derivatives on the diameter of renal arterioles to determine the structural requirements of the vasoconstrictor response to 20-HETE. The vascular responses to 5-, 8-, 12-, 15-, 19-, 20-, 21-HETEs, arachidonic acid (AA), and saturated, partially saturated, dimethyl, carboxyl, and 19-carbon derivatives of 20-HETE (10(-8) to 10(-6) M) were assessed in rat renal interlobular arteries (65-125 micrometer). 20-HETE, 21-HETE, dimethyl-20-HETE, and a partially saturated derivative of 20-HETE, 20-hydroxyeicosa-5(Z),14(Z)-dienoic acid, reduced vessel diameter by 19 +/- 3, 17 +/- 3, 16 +/- 2, and 28 +/- 2%, respectively. In contrast, 5-, 8-, 12-, 15-, and 19-HETE, AA, saturated, partially saturated, carboxyl, and the 19-carbon derivatives of 20-HETE had no effect on vessel diameter. Pretreatment with 5-, 15-, and 19-HETE, the 19-carbon derivative or 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (1 microM) completely blocked the vasoconstrictor response to 20-HETE in renal arterioles. Pretreatment with AA, carboxyl, saturated 19-carbon, and saturated 20-HETE derivatives (1 microM) partially blocked the response, whereas 8- and 12-HETE (1 microM) had no effect on the vasoconstrictor response to 20-HETE. These findings suggest that 20-HETE agonists and antagonists require a carboxyl or an ionizable group on carbon 1 and a double bond near the 14 or 15 carbon. 20-HETE agonists also require a functional group capable of hydrogen bonding on carbon 20 or 21, whereas antagonists lack this reactive group.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, USA.
authors.forename: M
authors.initials: M
authors.lastname: Alonso-Galicia
authors.forename: J R
authors.initials: JR
authors.lastname: Falck
authors.forename: K M
authors.initials: KM
authors.lastname: Reddy
authors.forename: R J
authors.initials: RJ
authors.lastname: Roman
mesh_terms: D000818:Animals; D001158:Arteries / Q000187:drug effects; D006893:Hydroxyeicosatetraenoic Acids / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000737:chemistry; D017665:Hydroxyl Radical / Q000737:chemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects*; D014661:Vasoconstriction
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D017665:Hydroxyl Radical; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid