Churchill P C, Rossi N F, Churchill M C, Bidani A K, McDonald F D
Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Am J Physiol. 1990 Jan;258(1 Pt 2):F41-5. doi: 10.1152/ajprenal.1990.258.1.F41.
Both acute and chronic administration of cyclosporine A (CSA) lead to renal vasoconstriction, but the mechanism is not fully understood. The present studies were designed to explore the possible role of adenosine in acute CSA-induced renal vasoconstriction in rats. Six groups of anesthetized Sprague-Dawley rats were studied using standard clearance techniques: group 1 rats were controls; groups 2, 4, and 6 received CSA intravenously at 20, 30, and 40 mg.h-1.kg body wt-1, respectively; groups 3 and 5 were identical to groups 2 and 4 except that a priming injection of theophylline was given (56 mumol/kg body wt) and theophylline was included in the intravenous infusate (0.56 mumol.min-1.kg body wt-1). CSA produced acute and concentration-dependent reductions in renal plasma flow (left kidney) and in the clearances of p-aminohippuric acid and inulin (both kidneys). Except in group 6, these changes were observed in the absence of a decrease in arterial blood pressure, demonstrating that CSA produced an acute and concentration-dependent increase in renovascular resistance. Theophylline not only failed to block CSA-induced renal vasoconstriction, if anything, it potentiated it. Because theophylline is an adenosine receptor antagonist, these findings contradict the hypothesis that adenosine mediates acute CSA-induced renal vasoconstriction.
环孢素A（CSA）的急性和慢性给药均会导致肾血管收缩，但其机制尚未完全明确。本研究旨在探讨腺苷在急性CSA诱导的大鼠肾血管收缩中可能发挥的作用。采用标准清除技术对六组麻醉的Sprague-Dawley大鼠进行了研究：第1组大鼠为对照组；第2、4和6组大鼠分别以20、30和40 mg·h⁻¹·kg体重⁻¹的剂量静脉注射CSA；第3和5组与第2和4组相同，只是预先注射了氨茶碱（56 μmol/kg体重），并且在静脉输注液中加入了氨茶碱（0.56 μmol·min⁻¹·kg体重⁻¹）。CSA导致肾血浆流量（左肾）以及对氨基马尿酸和菊粉清除率（双肾）出现急性且浓度依赖性降低。除第6组外，这些变化均在动脉血压未降低的情况下观察到，表明CSA导致肾血管阻力出现急性且浓度依赖性增加。氨茶碱不仅未能阻断CSA诱导的肾血管收缩，反而在一定程度上增强了这种收缩。由于氨茶碱是一种腺苷受体拮抗剂，这些发现与腺苷介导急性CSA诱导的肾血管收缩这一假说相矛盾。
