Johns E J
Br J Pharmacol. 1985 Mar;84(3):707-13. doi: 10.1111/j.1476-5381.1985.tb16153.x.
The effect of intravenous administration of the calcium-entry blocking drugs, diltiazem and nifedipine, on renal haemodynamic and tubular function was examined in denervated kidneys of pentobarbitone-anaesthetized rats. Infusion of vehicle for the compounds had no effect on renal function which was stable for the duration of the experiments. Diltiazem was infused at 5, 10 and 20 micrograms kg-1 min-1. Blood pressure did not change following 5 micrograms kg-1 min-1 diltiazem but was significantly reduced, by 12 mmHg, after 10 micrograms kg-1 min-1 and by 17 mmHg after 20 micrograms kg-1 min-1. Renal blood flow was not affected by any dose of diltiazem while at the lowest dose of drug, glomerular filtration rate (g.f.r.) was significantly increased, by 24%. Absolute and fractional sodium excretion were increased significantly, 154% and 77% respectively, by 5 micrograms kg-1 min-1 diltiazem, 20% and 24% respectively, by 10 micrograms kg-1 min-1 diltiazem, but were unchanged by 20 micrograms kg-1 min-1. Infusion of nifedipine at 0.5, 1.0 and 2.0 micrograms kg-1 min-1 decreased systemic blood pressure by 9, 9 and 20 mmHg, respectively. Renal blood flow was increased (7%) by 1.0 microgram kg-1 min-1 only, while g.f.r. did not change at any dose. Urine flow, absolute and fractional sodium excretions were increased, 127%, 96% and 90% respectively, by 0.5 microgram kg-1 min-1 nifedipine, 127%, 197% and 194% respectively, by 1.0 microgram kg-1 min-1, while these variables remained unchanged by a dose of 2.0 micrograms kg-1 min-1. 6 These data show that doses on diltiazem and nifedipine, which had little or no effect on blood pressure, had minimal actions on renal haemodynamics. However, at 5 and 10 jig kg-1 min- diltiazem and 0.5 and 1.0 jig kg-' min-' nifedipine these compounds exhibited direct tubular actions, causing both a diuresis and natriuresis, while at the highest dose of each drug these actions were masked by a concomitant reduction in blood pressure.
在戊巴比妥麻醉大鼠的去神经支配肾脏中，研究了静脉注射钙通道阻滞剂地尔硫䓬和硝苯地平对肾脏血流动力学和肾小管功能的影响。注射药物赋形剂对肾功能无影响，在实验期间肾功能保持稳定。以5、10和20微克/千克·分钟-1的速度输注地尔硫䓬。输注5微克/千克·分钟-1地尔硫䓬后血压未改变，但输注10微克/千克·分钟-1地尔硫䓬后血压显著降低12 mmHg，输注20微克/千克·分钟-1地尔硫䓬后血压降低17 mmHg。任何剂量的地尔硫䓬均不影响肾血流量，而在最低剂量时，肾小球滤过率（GFR）显著增加24%。5微克/千克·分钟-1地尔硫䓬使钠排泄绝对值和排泄分数分别显著增加154%和77%，10微克/千克·分钟-1地尔硫䓬使其分别增加20%和24%，但20微克/千克·分钟-1地尔硫䓬对其无影响。以0.5、1.0和2.0微克/千克·分钟-1输注硝苯地平分别使全身血压降低9 mmHg、9 mmHg和20 mmHg；仅1.0微克/千克·分钟-1的硝苯地平使肾血流量增加7%，而任何剂量下GFR均未改变；0.5微克/千克·分钟-1硝苯地平使尿流量、钠排泄绝对值和排泄分数分别增加127%、96%和90%，1.0微克/千克·分钟-1硝苯地平使其分别增加127%、197%和194%，而2.0微克/千克·分钟-1剂量下这些指标未改变.这些数据表明，对地尔硫䓬和硝苯地平而言，对血压影响很小或无影响的剂量对肾脏血流动力学影响也最小。然而，在5和10微克/千克·分钟-1地尔硫䓬以及0.5和1.0微克/千克·分钟-1硝苯地平剂量下，这些化合物表现出直接肾小管作用，导致利尿和利钠，而在每种药物最高剂量时，这些作用被伴随出现血压降低所掩盖。
