Steen P A, Milde J H, Gronert G A
J Pharmacol Exp Ther. 1983 Mar;224(3):594-7.
Kidney metabolites were studied in five anesthetized dogs before and after 5 mg/kg i.v. of ethacrynic acid, followed by 3 mg X kg-1 X hr-1. This dose, which inhibits most of the reabsorption of sodium and chloride in the diluting segment, improved the energy state in biopsies from the outer medulla and caused an increase in ATP and a decrease in ADP and AMP levels and the lactate/pyruvate ratio. This was probably related to ongoing rapid metabolism in the control biopsies (with improved results after ethacrynic acid due to a primary reduction in an ATP requiring process) before they were completely frozen in liquid nitrogen. No changes occurred in ATP, ADP or phosphocreatine levels or the lactate/pyruvate ratio in cortical biopsies, which was in agreement with the previously shown lack of effect on proximal tubular reabsorption at this dosage of ethacrynic acid. These results indicate that the saluretic effect and parallel reduction in outer medullary metabolic rate with ethacrynic acid cannot be due to a direct inhibition of mitochondrial ATP production as suggested by others from in vitro experiments. The reduced rate of ATP production in vivo must be secondary to a reduced ATP demand.
在五只麻醉犬静脉注射5mg/kg依他尼酸前后对肾脏代谢物进行了研究，随后以3mg·kg⁻¹·hr⁻¹的剂量给药。该剂量抑制了稀释段中大部分钠和氯的重吸收，改善了外髓活检组织的能量状态，导致ATP增加，ADP和AMP水平以及乳酸/丙酮酸比值降低。这可能与对照活检组织中持续的快速代谢有关（依他尼酸给药后结果改善，这是由于需要ATP的过程初步减少），然后它们被完全冷冻在液氮中。皮质活检组织中的ATP、ADP或磷酸肌酸水平以及乳酸/丙酮酸比值没有变化，这与之前显示的该剂量依他尼酸对近端小管重吸收无影响一致。这些结果表明，依他尼酸的利钠作用以及外髓代谢率的平行降低并非如其他人从体外实验所暗示的那样，是由于对线粒体ATP产生的直接抑制。体内ATP产生速率的降低必定继发于ATP需求的减少。
