Prasad N, Clarkson P B, MacDonald T M, Ryan M, Struthers A D, Thompson C J
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, University of Dundee, UK.
Diabet Med. 1998 Aug;15(8):678-82. doi: 10.1002/(SICI)1096-9136(199808)15:8<678::AID-DIA639>3.0.CO;2-K.
Raised plasma concentrations of atrial natriuretic peptide (ANP) have been reported in patients with Type 1 (insulin dependent) diabetes mellitus (DM) who have poor glycaemic control and are associated with the presence of microalbuminuria. To test the hypothesis that elevations in plasma ANP concentration increase urinary albumin excretion in Type 1 DM, we have studied the effects of intravenous infusions of ANP in eight such subjects with established microalbuminuria. Blood glucose was maintained between 4 and 7 mmol l-1 in all subjects for the duration of studies; after euglycaemia had been established, a standard oral water load (20 ml kg-1 plus replacement of urinary losses) was given. Once steady state diuresis was attained, subjects received intravenous infusion of either placebo (0.9% saline), low dose (2.5 pmol kg-1 min-1) or high dose (5.0 pmol kg-1 kg min-1) ANP solution in a randomized, double-blind protocol. Infusion of ANP caused a dose-dependent increase in urinary albumin excretion rate (placebo, 11.3 (SD 8.9) to 8.7 (SD 6.8) micrograms min-1; low dose ANP, 12.4 (SD 9.9) to 26.5 (SD 27.5) micrograms min-1, p < 0.01; high dose ANP 10.3 (SD 7.3) to 36.6 (SD 28.5) micrograms min-1, p < 0.001, ANOVA). Only high dose ANP caused an increase in urine flow. Blood glucose remained unchanged in all studies. We conclude that intravenous infusions of ANP cause a dose-dependent increase in urinary albumin excretion rate in Type 1 DM subjects with microalbuminuria. These data support the hypothesis that ANP has albuminuric actions which may contribute to microalbuminuria in Type 1 DM.
据报道，1型（胰岛素依赖型）糖尿病（DM）患者若血糖控制不佳且伴有微量白蛋白尿，则其血浆心房利钠肽（ANP）浓度会升高。为验证1型糖尿病患者血浆ANP浓度升高会增加尿白蛋白排泄这一假说，我们对8名已确诊微量白蛋白尿的此类患者进行了静脉输注ANP的研究。在研究期间，所有受试者的血糖维持在4至7 mmol l-1之间；血糖正常后，给予标准口服水负荷（20 ml kg-1加上补充尿失水量）。一旦达到稳定利尿状态，受试者按照随机、双盲方案接受静脉输注安慰剂（0.9%生理盐水）、低剂量（2.5 pmol kg-1 min-1）或高剂量（5.0 pmol kg-1 kg min-1）ANP溶液。输注ANP导致尿白蛋白排泄率呈剂量依赖性增加（安慰剂组，从11.3（标准差8.9）至8.7（标准差6.8）微克每分钟；低剂量ANP组，从12.4（标准差9.9）至26.5（标准差27.5）微克每分钟，p < 0.01；高剂量ANP组，从10.3（标准差7.3）至36.6（标准差28.5）微克每分钟，p < 0.001，方差分析）。只有高剂量ANP导致尿量增加。所有研究中血糖均保持不变。我们得出结论，静脉输注ANP会使1型糖尿病微量白蛋白尿患者的尿白蛋白排泄率呈剂量依赖性增加。这些数据支持了ANP具有致蛋白尿作用，可能导致1型糖尿病微量白蛋白尿的假说。
