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 t he tubuloglomerular feedback (TGF) response was examined. Under contro l conditions stop-flow pressure (SFP) fell by 17.0 +/- 2.1 mmHg when t he perfusion rate of the loop of Henle was increased from 0 to 50 nl/m in. Addition of AA (50 mu M) to the perfusate lowered basal SFP by 11. 4 +/- 1.1 mmHg and potentiated the TGF response. This effect was block ed by addition of a P-450 inhibitor, 17-octadecynoic acid (17-ODYA) (1 0 mu M), 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 b y 80%. After blockade of endogenous P-450 activity with 17-ODYA, addit ion of 20-hydroxyeicosatetraenoic acid (20-HETE, 10 mu M) to the perfu sate 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 mu M) The se results indicate that endogenous P-450 metabolites of AA, particula rly 20-HETE, may play a role in TGF and the regulation of renal vascul ar tone.