Lieberman J S, Parra L, Newton L, Scandling J D, Loon N, Myers B D
Department of Medicine, Stanford University Medical Center, CA 94305.
Diabetes. 1991 Jul;40(7):893-901. doi: 10.2337/diab.40.7.893.
We evaluated the renal and hormonal responses to volume expansion induced by water immersion in subjects with diabetic nephropathy (n = 12) and in healthy control subjects (n = 9). Immersion induced similar average increments in sodium excretion (+/- 223 vs. 176 mumol/min) and comparable decrements in renovascular resistance (RVR; -15 vs. -16 U). However, whereas the control subjects responded uniformly, the response among diabetic subjects was highly variable, with a subset of patients exhibiting paradoxical antinatriuresis and vasoconstriction. Immersion was associated with marked elevation of atrial natriuretic peptide (ANP) in plasma of diabetic versus control subjects (61 +/- 9 vs. 19 +/- 2 pM, respectively; P less than 0.001). Yet for each picomolar increment in plasma ANP during immersion, the corresponding increases in urinary excretion of cyclic guanosine monophosphate (26 vs. 279 pmol/min) and sodium (9 vs. 47 mumol/min) and the reciprocal lowering of RVR (0.7 vs. 1.9 U) were blunted in the diabetic versus control group. Volume contraction in the postimmersion period was associated with disproportionate antinatriuresis and renal vasoconstriction in the diabetic group, despite a persistent elevation of ANP (29 +/- 2 vs. 16 +/- 2 pM, P less than 0.01). We propose that renal insensitivity to ANP in diabetic nephropathy could contribute to altered vasoreactivity and abnormal excretory responsiveness to changing plasma volume. Blunted natriuresis in response to ANP release and enhanced sodium retention during volume contraction could account for the expanded extracellular fluid volume that has consistently been reported to accompany the development of diabetic nephropathy.
我们评估了糖尿病肾病患者（n = 12）和健康对照者（n = 9）对水浸诱导的容量扩张的肾脏和激素反应。水浸诱导钠排泄的平均增加量相似（±223对176 μmol/分钟），肾血管阻力（RVR）的降低程度相当（-15对-16 U）。然而，虽然对照者反应一致，但糖尿病患者中的反应高度可变，一部分患者表现出反常的钠潴留和血管收缩。与对照者相比，水浸与糖尿病患者血浆中心房利钠肽（ANP）的显著升高有关（分别为61±9对19±2 pM；P<0.001）。然而，在水浸期间，血浆ANP每增加1皮摩尔，糖尿病组与对照组相比，环磷酸鸟苷的尿排泄相应增加量（26对279 pmol/分钟）、钠的相应增加量（9对47 μmol/分钟）以及RVR的相应降低量（0.7对1.9 U）均减弱。尽管ANP持续升高（29±2对16±2 pM，P<0.01），但糖尿病组在浸后期间的容量收缩与不成比例的钠潴留和肾血管收缩有关。我们提出，糖尿病肾病中肾脏对ANP不敏感可能导致血管反应性改变以及对血浆容量变化的排泄反应异常。对ANP释放反应的钠利尿减弱以及容量收缩期间钠潴留增强可能解释了一直报道的伴随糖尿病肾病发展的细胞外液容量扩张。
