Faculty Collaboration Database

Epoxyeicosatrienoic acids, 20-hydroxyeicosatetraenoic acid, and renal microvascular function. Prostaglandins Other Lipid Mediat 2013;104-105:2-7

Date

01/22/2013

Pubmed ID

23333581

Pubmed Central ID

PMC3664103

DOI

10.1016/j.prostaglandins.2013.01.002

Scopus ID

2-s2.0-84879685602 (requires institutional sign-in at Scopus site)   59 Citations

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.

Author List

Imig JD

MESH terms used to index this publication - Major topics in bold

8,11,14-Eicosatrienoic Acid
Arachidonic Acid
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System
Endothelial Cells
Endothelium, Vascular
Epoxide Hydrolases
Humans
Hydroxyeicosatetraenoic Acids
Hypertension, Renal
Kidney
Large-Conductance Calcium-Activated Potassium Channels
Microcirculation
Small Molecule Libraries
Vasoconstriction
Vasodilation