López-Novoa J M, Montañés I
Departamento de Fisiologia and Farmacologia, Facultad de Medicina, Universidad de Salamanca, Spain.
Can J Physiol Pharmacol. 1993 Oct-Nov;71(10-11):848-53. doi: 10.1139/y93-127.
The aim of this study was to evaluate the effects of the two enantiomers of a new dihydropyridine, S12967 and S12968, on rat renal function. Male Wistar rats were injected intravenously with saline, S12967, or S12968 (0.1, 0.3, or 1 mg/kg body weight). Urinary flow, glomerular filtration rate, renal plasma flow, urinary sodium, potassium, and calcium excretions, mean arterial pressure, and renal vascular resistance were determined before and every 30 min up to 180 min after administration of the tested substance. The levogyre enantiomer S12968, at a dose of 0.3 mg/kg, induced a 4-fold increase in urinary sodium excretion, without significant or with minor changes in glomerular filtration rate, renal plasma flow, or renal blood flow. The hypotensive effect was small and nonsignificant. At 1 mg/kg, S12968 caused a profound hypotensive effect that impaired the renal function, induced marked oliguria, and decreased glomerular filtration rate and renal blood flow to almost negligible values. The dextrogyre enantiomer S12967 had much less effect on renal function. These data showing specific stereoselective renal effects are in agreement with pharmacological studies that have demonstrated that S12968 possesses a higher affinity for the dihydropyridine-binding site than its dextrogyre enantiomer, S12967.
本研究的目的是评估一种新型二氢吡啶的两种对映体S12967和S12968对大鼠肾功能的影响。将雄性Wistar大鼠静脉注射生理盐水、S12967或S12968（0.1、0.3或1mg/kg体重）。在给予受试物质之前以及给药后每30分钟直至180分钟，测定尿流量、肾小球滤过率、肾血浆流量、尿钠、钾和钙排泄量、平均动脉压以及肾血管阻力。左旋对映体S12968，剂量为0.3mg/kg时，可使尿钠排泄增加4倍，而肾小球滤过率、肾血浆流量或肾血流量无显著变化或仅有轻微变化。降压作用较小且不显著。在1mg/kg时，S12968引起显著的降压作用，损害肾功能，导致明显少尿，并使肾小球滤过率和肾血流量降至几乎可忽略不计的值。右旋对映体S12967对肾功能的影响小得多。这些显示出特定立体选择性肾效应的数据与药理学研究一致，药理学研究表明S12968对二氢吡啶结合位点的亲和力高于其右旋对映体S12967。
