van der Zander K, Houben A J H M, Webb D J, Udo E, Kietselaer B, Hofstra L, De Mey J G R, de Leeuw P W
Department of Medicine, Cardiovascular Research Institute Maastricht (CARIM) and University Hospital Maastricht, P. Debyelaan 25, 6202 AZ Maastricht, The Netherlands.
Kidney Int. 2006 Mar;69(5):864-8. doi: 10.1038/sj.ki.5000215.
Brain natriuretic peptide (BNP) and endothelin-1 (ET-1) both exhibit natriuretic activity within the human kidney. Furthermore, they both act partly through activation of the endothelial nitric oxide pathway. Since ET-1 may cause vasodilation and natriuresis via stimulation of the ET-B receptor, the aim of the present study was to investigate whether renal ET-B receptors participate in the renal actions of BNP. In this placebo-controlled, crossover study, we infused BNP (4 pmol/kg/min) or placebo (i.v.) for 1 h, with or without co-infusion of the ET-B receptor antagonist BQ-788 (50 nmol/min) for 15 min on 4 separate days, in 10 healthy subjects (mean age 54+/-6 years.). During infusion, we measured effective renal plasma flow (ERPF), and glomerular filtration rate (GFR) using PAH/inulin clearance. Cardiac output was measured before and after infusion, using echocardiography. Blood pressure and heart rate (HR) were monitored as well. Urine and plasma samples were taken every hour to measure diuresis, natriuresis, cyclic 3',5' guanosine monophosphate, and ET-1 levels. BNP with or without ET-B receptor blockade increased natriuresis and diuresis. In addition, BNP alone increased GFR and filtered load, without changing ERPF. BQ-788 infusion did not affect renal hemodynamics or natriuresis. Neither BNP nor BQ-788 altered cardiac output, blood pressure, and heart rate. In conclusion, the present study shows that selective ET-B receptor blockade has no effect on the BNP-induced natriuresis and glomerular filtration rate.
脑钠肽（BNP）和内皮素 -1（ET -1）在人体肾脏内均表现出利钠活性。此外，它们都部分通过激活内皮一氧化氮途径发挥作用。由于ET -1可通过刺激ET -B受体引起血管舒张和利钠作用，本研究的目的是调查肾脏ET -B受体是否参与BNP的肾脏作用。在这项安慰剂对照的交叉研究中，我们在10名健康受试者（平均年龄54±6岁）中，于4个不同日期，静脉输注BNP（4 pmol/kg/分钟）或安慰剂1小时，同时在其中15分钟内联合输注ET -B受体拮抗剂BQ -788（50 nmol/分钟）。输注期间，我们使用对氨基马尿酸/菊粉清除率测量有效肾血浆流量（ERPF）和肾小球滤过率（GFR）。使用超声心动图在输注前后测量心输出量。同时监测血压和心率（HR）。每小时采集尿液和血浆样本以测量尿量、尿钠排泄、环磷酸鸟苷和ET -1水平。无论有无ET -B受体阻断，BNP均可增加尿钠排泄和尿量。此外，单独使用BNP可增加GFR和滤过负荷，而不改变ERPF。输注BQ -788不影响肾脏血流动力学或尿钠排泄。BNP和BQ -788均未改变心输出量、血压和心率。总之，本研究表明选择性ET -B受体阻断对BNP诱导的尿钠排泄和肾小球滤过率无影响。
