Bidani A K, Churchill P C, Packer W
Can J Physiol Pharmacol. 1987 Jan;65(1):42-5. doi: 10.1139/y87-008.
We have reported previously that aminophylline has an ameliorating effect on the course and severity of glycerol-induced myoglobinuric acute renal failure in rats. Since aminophylline dissociates into theophylline in biological fluids and since theophylline is an adenosine receptor antagonist, we attributed the ameliorating effects to antagonism of the hemodynamic effects of endogenous adenosine. However, theophylline blocks tubuloglomerular feedback and produces natriuresis, and either of these effects might have accounted for the beneficial effects in acute renal failure. Therefore, this study was designed to further characterize the effects of theophylline in glycerol-induced acute renal failure in rats. Aminophylline had dose-dependent beneficial effects, as judged by the peak serum creatinine during the 3 days following induction of acute renal failure, by the number of animals with peak serum creatinine greater than 1 mg/dL, and by the mortality rate. Both furosemide and theophylline block tubuloglomerular feedback and produce natriuresis, but aminophylline had protective effects, whereas furosemide actually increased mortality, compared with aminophylline, following induction of myoglobinuric acute renal failure. Therefore, aminophylline's protective effects are independent of tubuloglomerular feedback and natriuresis. These results offer further support for the hypothesis that adenosine-induced hemodynamic changes play a pathogenic role in glycerol-induced acute renal failure in rats.
我们之前报道过，氨茶碱对甘油诱导的大鼠肌红蛋白尿性急性肾衰竭的病程和严重程度具有改善作用。由于氨茶碱在生物体液中会解离成茶碱，且茶碱是一种腺苷受体拮抗剂，我们将这种改善作用归因于对内源性腺苷血流动力学效应的拮抗作用。然而，茶碱会阻断肾小管球反馈并产生利钠作用，这些作用中的任何一种都可能是急性肾衰竭中有益效应的原因。因此，本研究旨在进一步明确茶碱在甘油诱导的大鼠急性肾衰竭中的作用。根据急性肾衰竭诱导后3天内的血清肌酐峰值、血清肌酐峰值大于1mg/dL的动物数量以及死亡率判断，氨茶碱具有剂量依赖性的有益作用。速尿和茶碱都会阻断肾小管球反馈并产生利钠作用，但与氨茶碱相比，在诱导肌红蛋白尿性急性肾衰竭后，氨茶碱具有保护作用，而速尿实际上增加了死亡率。因此，氨茶碱的保护作用独立于肾小管球反馈和利钠作用。这些结果为腺苷诱导的血流动力学变化在甘油诱导的大鼠急性肾衰竭中起致病作用这一假说提供了进一步支持。
