Yagil Y
Department of Medicine, University of Rochester, New York 14642.
Am J Physiol. 1990 May;258(5 Pt 2):F1139-44. doi: 10.1152/ajprenal.1990.258.5.F1139.
Acute cyclosporin A (CysA) nephrotoxicity has been attributed to intrarenal vasoconstriction. It has been previously demonstrated that CysA decreases whole kidney and cortical blood flow. The effect of CysA on medullary blood flow has not been adequately studied, despite the high susceptibility of structures in the renal medulla to ischemia and the common use of CysA after the kidney is subjected to transient ischemia. To determine its effects on medullary blood flow in the normal and postischemic kidney, CysA was administered acutely in anesthetized Munich-Wistar rats at doses ranging from 4 to 20 mg/kg. Total renal blood flow (TRBF) and glomerular filtration rate (GFR) were determined in normal kidneys (group 1) by standard clearance techniques before and after infusion of CysA. In animals subjected to 40-min unilateral renal ischemia (group 2) TRBF was measured with an electromagnetic flowmeter. Vasa recta blood flow was determined in both groups by fluorescence videomicroscopy. In group 1, infusion with 20 mg/kg CysA, but not with 4 or 8 mg/kg, increased renal vascular resistance (RVR) and decreased TRBF. GFR was not affected and filtration fraction increased. Vasa recta blood flow was not significantly altered. In group 2, 20 mg/kg CysA increased RVR and decreased TRBF. Vasa recta blood flow decreased significantly in the descending but not in the ascending vasa recta. These results suggest that, in the normal kidney, vasa recta blood flow in the renal medulla is not affected by acute administration of CysA, whereas in the postischemic kidney, CysA decreases blood flow preferentially in the descending vasa recta, in proportion to the decline in TRBF.
急性环孢素A(CysA)肾毒性被认为与肾内血管收缩有关。此前已证实,CysA会降低全肾和皮质血流量。尽管肾髓质结构对缺血高度敏感,且在肾脏经历短暂缺血后常使用CysA,但CysA对髓质血流量的影响尚未得到充分研究。为了确定其对正常和缺血后肾脏髓质血流量的影响,在麻醉的慕尼黑-威斯塔大鼠中急性给予CysA,剂量范围为4至20mg/kg。通过标准清除技术在输注CysA前后测定正常肾脏(第1组)的总肾血流量(TRBF)和肾小球滤过率(GFR)。在经历40分钟单侧肾缺血的动物(第2组)中,用电磁流量计测量TRBF。通过荧光视频显微镜测定两组的直小血管血流量。在第1组中,输注20mg/kg CysA而非4或8mg/kg会增加肾血管阻力(RVR)并降低TRBF。GFR未受影响,滤过分数增加。直小血管血流量无明显改变。在第2组中,20mg/kg CysA增加了RVR并降低了TRBF。直小血管下行支血流量显著减少,而上行支未减少。这些结果表明,在正常肾脏中,急性给予CysA不会影响肾髓质直小血管血流量,而在缺血后肾脏中,CysA会优先降低直小血管下行支的血流量,与TRBF的下降成比例。