Vailly B, Barthelmebs M, Velly J, Grima M, Imbs J L
Institut de pharmacologie (URA DO 589 CNRS), université Louis-Pasteur, CHRU, Strasbourg.
Arch Mal Coeur Vaiss. 1990 Jul;83(8):1259-62.
The early renal effects associated with streptozotocin-induced diabetes in rats (glomerular hyperfiltration and increase in filtration fraction) are similar to modifications reported in the early stage of human diabetic nephropathy. We examined the reversibility of these early renal diabetic effects by dopamine, which might correct glomerular hyperfiltration thanks to its preferential vasodilatory action on glomerular efferent arterioles. A dopamine prodrug, L-dopa was used to increase endorenal dopamine synthesis. Studies were carried out on streptozotocin-treated (60 mg/kg, i.v.) Wistar rats, supplemented with NPH insulin (2 to 3 U/day) such as to stabilize hyperglycemia at 22 mmol/l. One week after diabetes induction, animals were treated during a week either with L-dopa (10 mg/kg, s.c. twice daily) or L-dopa plus a dopa-decarboxylase inhibitor, carbidopa (10 mg/kg, s.c. 30 min before each L-dopa injection) or L-dopa plus a selective D1 receptor antagonist, SCH 23390 (100 micrograms/kg, s.c., with each L-dopa injection). Control diabetic animals received the solvent of L-dopa and control non-diabetic animals received the solvent of streptozotocin. After one week of L-dopa or other treatment, the renal functions of the rats were investigated (polyfructosan and PAH clearances) under inactin anaesthesia. As expected, streptozotocin induced glomerular hyperfiltration (1.3 +/- 0.07, n = 14, versus 0.93 +/- 0.05 ml/min.g kidney weight in non-diabetic controls, p less than 0.001) and an increase in filtration fraction (52.4 +/- 5.1 versus 32.1 +/- 1.7%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
链脲佐菌素诱导的大鼠糖尿病相关的早期肾脏效应(肾小球超滤和滤过分数增加)类似于人类糖尿病肾病早期报道的改变。我们研究了多巴胺对这些早期糖尿病肾脏效应的可逆性,多巴胺可能因其对肾小球出球小动脉的优先血管舒张作用而纠正肾小球超滤。一种多巴胺前体药物L-多巴被用于增加肾脏内多巴胺的合成。实验在链脲佐菌素处理(60mg/kg,静脉注射)的Wistar大鼠身上进行,补充中性鱼精蛋白锌胰岛素(2至3U/天)以将高血糖稳定在22mmol/l。糖尿病诱导一周后,动物接受为期一周的治疗,分别为L-多巴(10mg/kg,皮下注射,每日两次)或L-多巴加多巴脱羧酶抑制剂卡比多巴(10mg/kg,在每次L-多巴注射前30分钟皮下注射)或L-多巴加选择性D1受体拮抗剂SCH 23390(100μg/kg,皮下注射,与每次L-多巴注射同时进行)。对照糖尿病动物接受L-多巴的溶剂,对照非糖尿病动物接受链脲佐菌素的溶剂。在L-多巴或其他治疗一周后,在戊巴比妥钠麻醉下研究大鼠的肾功能(多聚果糖和对氨基马尿酸清除率)。如预期的那样,链脲佐菌素诱导了肾小球超滤(1.3±0.07,n = 14,非糖尿病对照组为0.93±0.05ml/min·g肾重,p<0.001)和滤过分数增加(52.4±5.1对32.1±1.7%,p<0.01)。(摘要截短于250字)