Ortola F V, Ballermann B J, Brenner B M
Renal Division, Brigham and Women's Hospital, Boston, Massachusetts.
Am J Physiol. 1988 Dec;255(6 Pt 2):F1091-7. doi: 10.1152/ajprenal.1988.255.6.F1091.
Atrial natriuretic peptide (ANP) infusion increases fractional excretion of many solutes including sodium, chloride, bicarbonate, phosphate, calcium, and magnesium. Because fractional excretion of these solutes increases with advancing renal disease, and because plasma ANP levels are known to be elevated in chronic renal failure, we sought to determine whether ANP mediates increased solute excretion rates per nephron in rats following extensive renal ablation, a model of chronic renal failure. Because sodium restriction decreases plasma ANP levels in the setting of reduced renal mass, we also determined the effect of sodium restriction on sodium, phosphate, calcium, and magnesium excretion rates in rats with 5/6 nephrectomy (NX). We also assessed whether high endogenous ANP levels influence fractional sodium, phosphate, calcium, and magnesium excretion in rats with 5/6 NX, by inhibiting ANP action via infusion of a high-affinity ANP antiserum. Whole-kidney glomerular filtration rate in 5/6 NX rats averaged approximately one-third that of shams, and plasma ANP levels were significantly elevated in these rats above those of shams, but to a lesser extent in rats on low- vs. high-salt intakes. Fractional sodium, phosphate, and calcium, but not magnesium excretion rates were significantly greater in 5/6 NX rats on the higher sodium intake compared with those in 5/6 NX rats on the lower sodium intake. Moreover, in 5/6 NX rats on the higher sodium intake, ANP antiserum significantly reduced fractional sodium, phosphate, and calcium excretion, but was without effect on magnesium excretion. These data implicate endogenous ANP in promoting the adaptive increase in sodium, phosphate, calcium, but not magnesium excretion per nephron in chronic renal disease.
输注心房利钠肽（ANP）可增加包括钠、氯、碳酸氢盐、磷酸盐、钙和镁在内的多种溶质的排泄分数。由于这些溶质的排泄分数会随着肾脏疾病的进展而增加，并且已知慢性肾衰竭患者血浆ANP水平会升高，因此我们试图确定ANP是否介导了大鼠在广泛肾切除术后单个肾单位溶质排泄率的增加，广泛肾切除是一种慢性肾衰竭模型。由于在肾质量减少的情况下，限制钠摄入会降低血浆ANP水平，因此我们还确定了限制钠摄入对5/6肾切除（NX）大鼠钠、磷酸盐、钙和镁排泄率的影响。我们还通过输注高亲和力ANP抗血清抑制ANP作用，评估了高内源性ANP水平是否会影响5/6 NX大鼠钠、磷酸盐、钙和镁的排泄分数。5/6 NX大鼠的全肾肾小球滤过率平均约为假手术组的三分之一，这些大鼠的血浆ANP水平明显高于假手术组，但低盐摄入组大鼠的升高程度低于高盐摄入组。与低钠摄入的5/6 NX大鼠相比，高钠摄入的5/6 NX大鼠的钠、磷酸盐和钙排泄分数显著更高，但镁排泄率无显著差异。此外，在高钠摄入的5/6 NX大鼠中，ANP抗血清显著降低了钠、磷酸盐和钙的排泄分数，但对镁排泄无影响。这些数据表明，内源性ANP在促进慢性肾脏疾病中单个肾单位钠、磷酸盐、钙而非镁排泄的适应性增加中起作用。
