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

Ying Ge, Sydney R. Murphy, Yan Lu, J R Falck, Ruisheng Liu, Richard J. Roman

Research output: Contribution to journalArticle

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)42-48
Number of pages7
JournalProstaglandins and Other Lipid Mediators
Volume102-103
DOIs
StatePublished - 2013

Keywords

  • 20-HETE
  • Afferent arteriole
  • Myogenic response
  • Tubuloglomerular feedback

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

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