Druml W, Kelly R A, England B K, O'Hara D S, Mitch W E
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Kidney Int. 1990 Dec;38(6):1061-7. doi: 10.1038/ki.1990.313.
As abnormalities of active cation transport could contribute to the genesis of uremic cardiomyopathy, we investigated myocardial sodium pump function in rats with acute renal failure (ARF) and with a model of experimental chronic renal failure (CRF) that has metabolic similarities to advanced chronic uremia in humans. CRF rats were hypertensive and had left ventricular hypertrophy (33% higher heart:body weight ratio; P less than 0.01) at four weeks compared to pair-fed sham-operated rats. Importantly, both ouabain- and furosemide-sensitive 86Rb uptake rates were unchanged in left ventricular myocardial slices from CRF, and the intracellular sodium concentration was not different from that of control rats even though skeletal muscle sodium was increased, as we found previously (J Clin Invest 81:1197, 1988). Insulin-stimulated, ouabain-sensitive 86Rb influx was also preserved. There also were no abnormalities in myocardium cation transport in rats with ARF. However, [3H]ouabain binding was decreased 45% in CRF rats (P less than 0.01); it was unchanged in acute uremia. Decreased ouabain binding in chronic uremia was due entirely to fewer low affinity [3H]ouabain binding sites (the binding affinity for ouabain was unaffected). We conclude that in chronic, (but not acute) renal failure, sodium pump number is reduced in myocardium but intracellular sodium is unchanged and active cation flux rates are maintained. These results emphasize that in rats with chronic uremia, intracellular sodium homeostasis is preserved in myocardium, despite the presence of marked abnormalities of active cation transport in skeletal muscle that are characteristic of chronic uremia.
由于活性阳离子转运异常可能导致尿毒症性心肌病的发生，我们研究了急性肾衰竭（ARF）大鼠以及一种实验性慢性肾衰竭（CRF）模型大鼠的心肌钠泵功能，该模型在代谢方面与人类晚期慢性尿毒症相似。与配对饲养的假手术大鼠相比，CRF大鼠在四周时出现高血压，且左心室肥厚（心脏与体重比高33%；P<0.01）。重要的是，CRF大鼠左心室心肌切片中哇巴因和呋塞米敏感的86Rb摄取率均未改变，尽管如我们之前所发现的（《临床研究杂志》81:1197, 1988），骨骼肌钠增加，但细胞内钠浓度与对照大鼠并无差异。胰岛素刺激的、哇巴因敏感的86Rb内流也得以保留。ARF大鼠的心肌阳离子转运也没有异常。然而，CRF大鼠中[3H]哇巴因结合减少了45%（P<0.01）；在急性尿毒症中则未改变。慢性尿毒症中哇巴因结合减少完全是由于低亲和力[3H]哇巴因结合位点减少（哇巴因的结合亲和力未受影响）。我们得出结论，在慢性（而非急性）肾衰竭中，心肌钠泵数量减少，但细胞内钠未改变，活性阳离子通量率得以维持。这些结果强调，在慢性尿毒症大鼠中，尽管存在慢性尿毒症特有的骨骼肌活性阳离子转运明显异常，但心肌中的细胞内钠稳态得以保留。
