Zou A P, Imig J D, Ortiz de Montellano P R, Sui Z, Falck J R, Roman R J
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226.
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.
研究了花生四烯酸（AA）的内源性P-450代谢产物对肾小管-肾小球反馈（TGF）反应的作用。在对照条件下，当髓袢灌注速率从0增加到50 nl/min时，停流压力（SFP）下降了17.0±2.1 mmHg。向灌注液中添加AA（50μM）可使基础SFP降低11.4±1.1 mmHg，并增强TGF反应。向灌注液中添加P-450抑制剂17-十八碳炔酸（17-ODYA）（10μM）可阻断这种作用。用17-ODYA灌注髓袢可使基础SFP升高3.7±0.3 mmHg，并使TGF反应降低80%。在用17-ODYA阻断内源性P-450活性后，向灌注液中添加20-羟基二十碳四烯酸（20-HETE，10μM）可使SFP出现流量依赖性下降。用甲氯芬那酸（2 mg/kg静脉注射）预处理动物或用呋塞米（50μM）灌注肾单位节段，均不改变20-HETE的作用。这些结果表明，AA的内源性P-450代谢产物，尤其是20-HETE，可能在TGF及肾血管张力调节中发挥作用。
