Effect of cyclosporine on the diluting capacity of the rat kidney.
Micropuncture experiments were carried out on rat kidneys in order to analyze the diluting ability of the thick ascending limb of Henle's loop (TAL) after acute and chronic administration of cyclosporine. Male albino Wistar rats weighing 190 to 250 g were either given cyclosporine (CSA) orally for 10 days or received single i.v. infusions of the drug before the micropuncture experiments. Drug free vehicle was administered to animals of two respective control groups. The electrolyte concentration of fluid from individual TALs was measured by continuous conductivity monitoring of early distal tubular fluid during pulse perfusion procedures. The transport dependent decrease of the electrolyte concentrations within the diluting segment showed a semi-logarithmic time course in all groups of rats. Lowest conductivity values were reached within 60 seconds of flow equilibrium in controls as well as in CSA treated rats. Chronic CSA feeding (15 mg/24 h/kg b.w., dissolved in 0.3 ml olive oil) as well as a single i.v. infusion of 5 mg/kg b.w. resulted in a significantly higher electrolyte concentration of TAL fluid. Infusion of the solvent alone was without significant effect on the diluting segment. We conclude that the impairment of the diluting ability of the TAL and hence the delivery of tubular fluid with increased NaCl concentrations to the macula densa should lead to a stimulation of the tubulo-glomerular feedback mechanism. Feedback activation per se could be the cause of the consistent GFR decrease and thus contribute to the basic nephrotoxicity of CSA.