title: Endogenously produced 20-HETE modulates myogenic and TGF response in microperfused afferent arterioles.
abstract: Previous studies have indicated that 20-hydroxyeicosatetraeonic acid (20-HETE) modulates vascular tone in large cerebral and renal arteries through inhibition of the large conductance, calcium sensitive potassium (BK) channel activity. However, the role of 20-HETE in modulating tubuloglomerular feedback (TGF) and the myogenic response in the afferent arteriole (Af-Art) is unknown. The present study examined the effects of inhibitors of the synthesis and action of 20-HETE on the myogenic and TGF responses of isolated rabbit and mouse Af-Arts. Luminal diameter decreased by 9.2±0.5% in mice and 8.9±1.3% in rabbit Af-Art when the perfusion pressure was increased from 60 to 120 mmHg. Administration of a 20-HETE synthesis inhibitor, HET0016 (1 μM), or a selective 20-HETE antagonist, 6, 15-20-hydroxyeicosadienoic acid (6, 15-20-HEDE, 10 μM) completely blocked the myogenic response of both rabbit and mouse Af-Art, while addition of 5, 14-20-HEDE (10 μM), a 20-HETE agonist, restored the myogenic response in vessels treated with HET0016. Increases in NaCl concentration from 10 to 80 mM of the solution perfusing the macula densa constricted the Af-Art of rabbits by 6.0±1.4 μm (n=5). Addition of a 20-HETE agonist to the tubular perfusate potentiated the TGF-mediated vasoconstrictor response. This response was blocked by addition of a 20-HETE antagonist (6, 15-20-HEDE, 10 μM) to the vascular perfusate. These studies indicate that locally produced 20-HETE plays an important role in modulating the myogenic and TGF responsiveness of the Af-Art and may help explain how deficiencies in the renal formation of 20-HETE could promote the development of hypertension induced glomerular injury.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ge
authors.forename: Sydney R
authors.initials: SR
authors.lastname: Murphy
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: John
authors.initials: J
authors.lastname: Falck
authors.forename: Ruisheng
authors.initials: R
authors.lastname: Liu
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Roman
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000378:metabolism; D001160:Arterioles / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000008:administration & dosage*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007606:Juxtaglomerular Apparatus / Q000098:blood supply / Q000187:drug effects*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects; D007684:Kidney Tubules / Q000098:blood supply* / Q000187:drug effects; D051379:Mice; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D010477:Perfusion; D011817:Rabbits
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid