Role of 20-HETE in the impaired myogenic and TGF responses of the Af-Art of Dahl salt-sensitive rats

Ying Ge, Sydney R. Murphy, Fan Fan, Jan Michael Williams, John R. Falck, Ruisheng Liu, Richard J. Roman

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20 Scopus citations

Abstract

The present study examined whether 20-HETE production is reduced in the renal vasculature and whether this impairs myogenic or tubuloglomerular feedback (TGF) responses of the afferent arteriole (Af-Art). The production of 20- HETE was 73% lower in renal microvessels of Dahl salt-sensitive rats (SS) rats than in SS.5BN rats, in which chromosome 5 from the Brown Norway (BN) rat containing the CYP4A genes was transferred into the SS genetic background. The luminal diameter of the Af-Art decreased by 14.7±1.5% in SS.5BN rats when the perfusion pressure was increased from 60 to 120 mmHg, but it remained unaltered in SS rats. Administration of an adenosine type 1 receptor agonist (CCPA, 1 μM) reduced the diameter of the Af-Art in the SS.5BN rats by 44±2%, whereas the diameter of the Af-Art of SS rats was unaltered. Autoregulation of renal blood flow (RBF) and glomerular capillary pressure (PGC) was significantly impaired in SS rats but was intact in SS.5BN rats. Administration of a 20-HETE synthesis inhibitor, HET0016 (1 μM), completely blocked the myogenic and adenosine responses in the Af-Art and autoregulation of RBF and PGC in SS.5BN rats, but it had no effect in SS rats. These data indicate that a deficiency in the formation of 20-HETE in renal microvessels impairs the reactivity of the Af-Art of SS rats and likely contributes to the development of hypertension induced renal injury.

Original languageEnglish (US)
Pages (from-to)F509-F515
JournalAmerican Journal of Physiology - Renal Physiology
Volume307
Issue number5
DOIs
StatePublished - Sep 1 2014

Keywords

  • Glomerulus
  • Myogenic response
  • Renal injury
  • TGF

ASJC Scopus subject areas

  • Physiology
  • Urology

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