Effect of P-450 omega-hydroxylase metabolites of arachidonic acid on tubuloglomerular feedback.
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.
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
A P
AP
Zou
J D
JD
Imig
P R
PR
Ortiz de Montellano
Z
Z
Sui
J R
JR
Falck
R J
RJ
Roman
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005246:Feedback; D005665:Furosemide / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000502:physiology; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009994:Osmolar Concentration; D010477:Perfusion; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley
D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; D008469:Meclofenamic Acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D005665:Furosemide; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C067516:arachidonic acid 18-hydroxylase