Kusaka H, Nomura H, Karasawa A
Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Jpn J Pharmacol. 1994 Sep;66(1):81-6. doi: 10.1254/jjp.66.81.
Effects of benidipine on urine volume, excretion of electrolytes and renal hemodynamics were investigated in anesthetized spontaneously hypertensive rats (SHR). Benidipine at 3 and 10 micrograms/kg (i.v.) significantly increased urine volume, sodium (Na) and potassium (K) excretion with no change of creatinine clearance (CCRE). The increase in K excretion was relatively slight when compared with that in Na excretion. In another series of experiments, the tubular sites of action of benidipine were determined by the lithium clearance (CLi) technique and the stop-flow method. Benidipine at 3 micrograms/kg (i.v.) increased CLi, decreased creatinine concentration and increased Na concentration in the stop-flow urine from the distal nephron. These results suggest that benidipine produces diuresis and natriuresis by the inhibition of water and Na reabsorption at both the proximal tubule and the distal nephron. Benidipine increased p-aminohippuric acid clearance, but not CCRE, at doses of 3 and 10 micrograms/kg (i.v.), suggesting that benidipine dilates the glomerular efferent arteriole as well as the afferent arteriole. It is, therefore, expected that benidipine does not cause intraglomerular hypertension and has a beneficial effect in progressive renal disease.
在麻醉的自发性高血压大鼠（SHR）中研究了贝尼地平对尿量、电解质排泄和肾血流动力学的影响。静脉注射3和10微克/千克的贝尼地平可显著增加尿量、钠（Na）和钾（K）排泄，而肌酐清除率（CCRE）无变化。与Na排泄增加相比，K排泄增加相对较小。在另一系列实验中，通过锂清除率（CLi）技术和停流法确定了贝尼地平的肾小管作用部位。静脉注射3微克/千克的贝尼地平可增加CLi，降低肌酐浓度，并增加远端肾单位停流尿液中的Na浓度。这些结果表明，贝尼地平通过抑制近端小管和远端肾单位的水和Na重吸收而产生利尿和利钠作用。静脉注射3和10微克/千克剂量的贝尼地平可增加对氨基马尿酸清除率，但不增加CCRE，提示贝尼地平可扩张肾小球出球小动脉和入球小动脉。因此，预计贝尼地平不会引起肾小球内高压，对进行性肾病具有有益作用。
