Effect of P-450 omega-hydroxylase metabolites of arachidonic acid on tubuloglomerular feedback

Am J Physiol. 1994 Jun;266(6 Pt 2):F934-41. doi: 10.1152/ajprenal.1994.266.6.F934.


The role of endogenous P-450 metabolites of arachidonic acid (AA) on the tubuloglomerular feedback (TGF) response was examined. Under control conditions stop-flow pressure (SFP) fell by 17.0 +/- 2.1 mmHg when the perfusion rate of the loop of Henle was increased from 0 to 50 nl/min. Addition of AA (50 microM) to the perfusate lowered basal SFP by 11.4 +/- 1.1 mmHg and potentiated the TGF response. This effect was blocked by addition of a P-450 inhibitor, 17-octadecynoic acid (17-ODYA) (10 microM), to the perfusate. Perfusion of the loop of Henle with 17-ODYA elevated basal SFP by 3.7 +/- 0.3 mmHg and reduced the TGF response by 80%. After blockade of endogenous P-450 activity with 17-ODYA, addition of 20-hydroxyeicosatetraenoic acid (20-HETE, 10 microM) to the perfusate produced a flow rate-dependent fall in SFP. The effect of 20-HETE was not altered by pretreating the animal with meclofenamate (2 mg/kg iv) or by perfusing the nephron segment with furosemide (50 microM). These results indicate that endogenous P-450 metabolites of AA, particularly 20-HETE, may play a role in TGF and the regulation of renal vascular tone.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arachidonic Acid / metabolism*
  • Arachidonic Acid / pharmacology
  • Cytochrome P-450 Enzyme System / metabolism*
  • Feedback
  • Furosemide / pharmacology
  • Hydroxyeicosatetraenoic Acids / pharmacology*
  • Kidney Glomerulus / drug effects*
  • Kidney Glomerulus / physiology
  • Kidney Tubules / drug effects*
  • Kidney Tubules / metabolism
  • Kidney Tubules / physiology
  • Male
  • Meclofenamic Acid / pharmacology
  • Mixed Function Oxygenases / metabolism*
  • Osmolar Concentration
  • Perfusion
  • Pressure
  • Rats
  • Rats, Sprague-Dawley


  • Hydroxyeicosatetraenoic Acids
  • Arachidonic Acid
  • Meclofenamic Acid
  • 20-hydroxy-5,8,11,14-eicosatetraenoic acid
  • Furosemide
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • arachidonic acid 18-hydroxylase