Fukui K, Tamaki T, Yamamoto A, Shoji T, Fujisawa Y, Iwao H, Abe Y
Department of Pharmacology, Kagawa Medical School, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 1987 Nov;336(5):572-7. doi: 10.1007/BF00169316.
In an attempt to define the effects of a calcium antagonist, nitrendipine, on renal function, intrarenal hemodynamics, and renin release, we infused the drug into the renal artery of anesthetized dogs. Infusion of nitrendipine at a rate of 5 micrograms/min in both hydropenic and hydrated dogs resulted in a significant increase in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow and renin release, with no change in systemic blood pressure, indicating a significant renal vasodilation. The urinary excretion rate of sodium increased by the same proportion as that of calcium. The intrarenal blood flow as measured by hydrogen washout rate showed that the outer cortical flow increased by the same proportion as the inner cortical flow. During nitrendipine infusion, free water reabsorption rate (TcH2O) in hydropenic dogs or free water clearance (CH2O) in hydrated dogs increased in proportion to the urine flow. Neither the ratio of TcH2O nor that of CH2O to osmolar clearance changed throughout the experiment. These data suggest that nitrendipine may not inhibit sodium transport in the medullary portion of the ascending limb of Henle and may induce an enhancement of the delivery of sodium to the Henle loop. Thus, nitrendipine exerts its diuretic and natriuretic actions via the alteration of renal hemodynamic and the inhibitory effect on proximal sodium reabsorption.
为了确定钙拮抗剂尼群地平对肾功能、肾内血流动力学和肾素释放的影响,我们将该药物注入麻醉犬的肾动脉。在缺水和水合的犬中,以5微克/分钟的速率输注尼群地平,导致肾血流量(RBF)、肾小球滤过率(GFR)、尿流量和肾素释放显著增加,而全身血压无变化,表明存在显著的肾血管舒张。钠的尿排泄率与钙的尿排泄率以相同比例增加。通过氢洗脱率测量的肾内血流量显示,外层皮质血流与内层皮质血流以相同比例增加。在输注尼群地平期间,缺水犬的自由水重吸收率(TcH2O)或水合犬的自由水清除率(CH2O)与尿流量成比例增加。在整个实验过程中,TcH2O与渗透清除率的比值以及CH2O与渗透清除率的比值均未改变。这些数据表明,尼群地平可能不会抑制亨氏袢升支髓质部的钠转运,并且可能会增强钠向亨氏袢的输送。因此,尼群地平通过改变肾血流动力学和对近端钠重吸收的抑制作用发挥其利尿和排钠作用。