Chan L, Chittinandana A, Shapiro J I, Shanley P F, Schrier R W
Department of Medicine, University of Colorado School of Medicine, Denver 80262.
Am J Physiol. 1994 Jan;266(1 Pt 2):F135-8. doi: 10.1152/ajprenal.1994.266.1.F135.
In the isolated perfused rat kidney, endothelin (ET) added to the perfusate at concentrations ranging from 50 to 500 pmol/l resulted in a dose-dependent reduction in renal perfusate flow (RPF) and inulin clearance (CIn). The decrease in RPF (17 +/- 3 vs. 34 +/- 3 ml.min-1 x g-1; P < 0.01 compared with control) and CIn (89 +/- 13 vs. 317 +/- 19 microliters.min-1 x g-1; P < 0.01 compared with control) by ET (500 pmol/l) was prevented by the ET antagonist BQ-123 (10 microM), with full recovery of RPF [36 +/- 2 vs. 34 +/- 3 ml.min-1 x g-1; not significant (NS) compared with control] and CIn (299 +/- 51 vs. 317 +/- 19 microliters.min-1 x g-1; NS compared with control). In the absence of ET, perfusion of the kidney with a similar concentration of BQ-123 (10 microM) did not induce any changes in RPF (36 +/- 5 vs. 34 +/- 3 ml.min-1 x g-1; NS compared with control) or CIn (320 +/- 14 vs. 317 +/- 19 microliters.min-1 x g-1; NS compared with control). After 60 min of arterial clamping, BQ-123 (10 microM) given before the onset of ischemia and during reflow improved CIn (88 +/- 4 vs. 19 +/- 3 microliters.min-1 x g-1; n = 6, P < 0.01) and net tubular sodium reabsorption (TNa) compared with no treatment. On the other hand, the same dose (10 microM) of BQ-123 given only during the reperfusion period was not effective in preventing the decreases in either CIn or TNa.(ABSTRACT TRUNCATED AT 250 WORDS)
在离体灌注大鼠肾脏中，向灌注液中添加浓度范围为50至500 pmol/l的内皮素（ET）会导致肾灌注液流量（RPF）和菊粉清除率（CIn）呈剂量依赖性降低。ET（500 pmol/l）使RPF降低（17±3对34±3 ml·min⁻¹·g⁻¹；与对照组相比P<0.01），CIn降低（89±13对317±19 μl·min⁻¹·g⁻¹；与对照组相比P<0.01），而ET拮抗剂BQ-123（10 μM）可防止这种降低，RPF完全恢复[36±2对34±3 ml·min⁻¹·g⁻¹；与对照组相比无显著差异（NS）]，CIn也恢复（299±51对317±19 μl·min⁻¹·g⁻¹；与对照组相比NS）。在无ET的情况下，用相似浓度（10 μM）的BQ-123灌注肾脏不会引起RPF（36±5对34±3 ml·min⁻¹·g⁻¹；与对照组相比NS）或CIn（320±14对317±19 μl·min⁻¹·g⁻¹；与对照组相比NS）的任何变化。在动脉夹闭60分钟后，在缺血开始前和再灌注期间给予BQ-123（10 μM）与未治疗相比可改善CIn（88±4对19±3 μl·min⁻¹·g⁻¹；n = 6，P<0.01）和肾小管钠重吸收净值（TNa）。另一方面，仅在再灌注期给予相同剂量（10 μM）的BQ-123在预防CIn或TNa降低方面无效。（摘要截短于250字）
