实验性糖尿病中多巴胺 D2 样受体阻断对肾小球高滤过的降低作用
Reduction of glomerular hyperfiltration by dopamine D(2)-like receptor blockade in experimental diabetes mellitus.
作者信息
Luippold G, Beilharz M, Mühlbauer B
机构信息
Department of Pharmacology, University of Tübingen, Tübingen, Germany.
出版信息
Nephrol Dial Transplant. 2001 Jul;16(7):1350-6. doi: 10.1093/ndt/16.7.1350.
BACKGROUND
Dopamine D(2)-like receptors are involved in the physiological response of renal haemodynamics to amino-acid infusion. The present study was performed to investigate whether domperidone, a D(2)-like receptor antagonist, modulates the pathological hyperfiltration in experimental diabetes mellitus.
METHODS
Renal function was studied in anaesthetized rats 2 weeks after induction of moderate diabetes mellitus by streptozotocin, and in non-diabetic controls. Rats in both groups continuously received domperidone or vehicle via drinking water. Following infusion of Ringer's saline for measurement of baseline values, an i.v. amino-acid load was applied to investigate the renal functional reserve.
RESULTS
In vehicle-treated diabetic rats baseline glomerular filtration rate and renal plasma flow were significantly higher compared with controls (1.10+/- 0.04 vs. 0.83+/-0.02 (P<0.004) and 4.83+/-0.26 vs 3.32+/-0.24 ml/min/100 g body weight (bw) (P<0.001) respectively). Domperidone completely normalized glomerular filtration rate and renal plasma flow in diabetic rats to values observed in vehicle-treated controls (0.81+/-0.07 (P=0.740) and 3.35+/- 0.30 ml/min/100 g bw (P=0.889) respectively). In the clearance experiments, arterial blood pressure, urinary flow rate and sodium excretion did not significantly differ when comparing the four groups. However, in conscious rats, urinary flow rate and sodium excretion were significantly higher in diabetic rats compared with non-diabetic controls. In both non-diabetic groups, amino-acid infusion induced a significant glomerular hyperfiltration that was completely absent in diabetic rats, and restored by domperidone treatment. In conscious vehicle-treated diabetic rats urinary albumin excretion was enhanced (449.0+/-47.7 vs. 185.7+/- 18.1 microg/24 h in non-diabetic rats (P<0.001)) and significantly lowered in diabetic rats by domperidone treatment (109.8+/-15.4 microg/24 h (P<0.001)).
CONCLUSION
The data suggest that dopaminergic mechanisms are involved in the changes in renal haemodynamics during early experimental diabetes mellitus in rats.
背景
多巴胺D(2)样受体参与肾脏血流动力学对氨基酸输注的生理反应。本研究旨在探讨D(2)样受体拮抗剂多潘立酮是否能调节实验性糖尿病中的病理性超滤。
方法
在链脲佐菌素诱导中度糖尿病2周后的麻醉大鼠以及非糖尿病对照大鼠中研究肾功能。两组大鼠均通过饮水持续接受多潘立酮或赋形剂。在输注林格氏液以测量基线值后，静脉注射氨基酸负荷以研究肾功能储备。
结果
在接受赋形剂治疗的糖尿病大鼠中，基线肾小球滤过率和肾血浆流量显著高于对照组（分别为1.10±0.04对0.83±0.02（P<0.004）以及4.83±0.26对3.32±0.24 ml/min/100 g体重（bw）（P<0.001））。多潘立酮使糖尿病大鼠的肾小球滤过率和肾血浆流量完全恢复正常，达到接受赋形剂治疗的对照组所观察到的值（分别为0.81±0.07（P=0.740）和3.35±0.30 ml/min/100 g bw（P=0.889））。在清除实验中，比较四组时动脉血压、尿流率和钠排泄无显著差异。然而，在清醒大鼠中，糖尿病大鼠的尿流率和钠排泄显著高于非糖尿病对照大鼠。在两个非糖尿病组中，氨基酸输注均诱导显著的肾小球超滤，而糖尿病大鼠中完全不存在这种超滤，多潘立酮治疗可使其恢复。在清醒的接受赋形剂治疗的糖尿病大鼠中，尿白蛋白排泄增加（449.0±47.7对非糖尿病大鼠的185.7±18.1 μg/24 h（P<0.001）），多潘立酮治疗使糖尿病大鼠的尿白蛋白排泄显著降低（109.8±15.4 μg/24 h（P<0.001））。
结论
数据表明多巴胺能机制参与大鼠早期实验性糖尿病期间肾脏血流动力学的变化。
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