Endogenously produced 20-HETE modulates myogenic and TGF response in microperfused afferent arterioles.

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.
AuthorsYing Ge, Sydney R Murphy, Yan Lu, John Falck, Ruisheng Liu, Richard J Roman
JournalProstaglandins & other lipid mediators (Prostaglandins Other Lipid Mediat) 2013 Apr-May Vol. 102-103 Pg. 42-8 ISSN: 1098-8823 [Print] United States
PMID23500064 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • Hydroxyeicosatetraenoic Acids
  • Arachidonic Acid
  • 20-hydroxy-5,8,11,14-eicosatetraenoic acid
  • Animals
  • Arachidonic Acid (administration & dosage, metabolism)
  • Arterioles (drug effects, physiology)
  • Blood Pressure (drug effects)
  • Humans
  • Hydroxyeicosatetraenoic Acids (administration & dosage)
  • Hypertension (drug therapy, physiopathology)
  • Juxtaglomerular Apparatus (blood supply, drug effects)
  • Kidney Glomerulus (blood supply, drug effects)
  • Kidney Tubules (blood supply, drug effects)
  • Mice
  • Microvessels (metabolism, pathology)
  • Perfusion
  • Rabbits

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