title: Epoxyeicosatrienoic acids, 20-hydroxyeicosatetraenoic acid, and renal microvascular function.
abstract: The development of pharmacological, genetic, and biochemical tools have allowed for detailed studies to determine the contribution of cytochrome P450 (CYP) metabolites of arachidonic acid to renal microvascular function. Renal microvessels can generate CYP hydroxylase metabolites including 20-hydroxyeicosatetraenoic acid (20-HETE) and CYP epoxygenase metabolites, epoxyeicosatrienoic acids (EETs). 20-HETE constricts afferent arterioles and contributes to renal blood flow autoregulation. EETs act as endothelium-dependent hyperpolarizing factors (EDHFs) on the renal microcirculation. 20-HETE inhibits whereas EETs activate renal microvascular smooth muscle cell large-conductance calcium-activated K(+) channels (KCa). Likewise, 20-HETE renal microvascular actions are pro-hypertensive and EET actions are anti-hypertensive. These findings in the renal microvasculature and those of others have provided impetus for the development of enzymatic inhibitors, agonists, and antagonists for 20-HETE and EETs to determine their potential therapeutic value. Initial genetic studies and experimental studies with soluble epoxide hydrolase inhibitors to increase EETs, EET analogs, and 20-HETE inhibitors have demonstrated improved renal microvascular function in hypertension. These findings have demonstrated the important contributions that 20-HETE and EETs play in the regulation of renal microvascular function.
authors: Department of Pharmacology & Toxicology, Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA. jdimig@mcw.edu
authors: John D
authors: JD
authors: Imig
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000378:metabolism* / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism* / Q000494:pharmacology; D006977:Hypertension, Renal / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D008833:Microcirculation / Q000187:drug effects; D054852:Small Molecule Libraries / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D006893:Hydroxyeicosatetraenoic Acids; D051036:Large-Conductance Calcium-Activated Potassium Channels; D054852:Small Molecule Libraries; D016718:Arachidonic Acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; D004851:Epoxide Hydrolases; D015126:8,11,14-Eicosatrienoic Acid