Johns E J, Manitius J
Br J Pharmacol. 1986 Sep;89(1):99-107. doi: 10.1111/j.1476-5381.1986.tb11125.x.
In pentobarbitone-anaesthetized rats, intravenous administration of diltiazem at 5 micrograms kg-1 min-1 did not change blood pressure or renal blood flow but increased glomerular filtration rate by approximately 16%, urine flow by 85%, calcium excretion by 151% and absolute and fractional sodium excretions by 100% and 69%, respectively. A similar pattern of responses was obtained in renally denervated animals, except that calcium excretion did not change statistically. Diltiazem given at 20 micrograms kg-1 min-1 into renally innervated and denervated groups of animals depressed blood pressure between 15-17 mmHg but had no effect on renal haemodynamic or tubular function. Nitrendipine administered at 0.5 microgram kg-1 min-1 to renally innervated and denervated animals significantly depressed blood pressure in intact animals by 6 mmHg and in both groups did not change renal haemodynamics but caused similar increases in urine flow of between 79-98%, calcium excretion of between 87 and 125%, absolute sodium excretion of between 108 and 140% and fractional sodium excretion of between 83 and 170%. Infusion of nitrendipine at 1.0 micrograms kg-1 min-1 into intact or renally denervated animals decreased blood pressure by 18-20 mmHg and increased urine flow by 84-111%, calcium excretion by 85%, absolute sodium excretion by 81-137% and fractional sodium excretion by 52-102%. Stimulation of the renal nerves at low frequencies (0.8 to 1.5 Hz) caused minimal changes in renal haemodynamics but decreased urine flow by 27%, calcium excretion by 35%, absolute and fractional sodium excretions 32% and 36%, respectively. In different groups of animals given either diltiazem at 20 pg kg- I min' or nitrendipine at 0.5 pg kg'- min' or 1.0 fg kg'- min', a similar degree of renal nerve stimulation caused an identical pattern of excretory responses of similar magnitude to those obtained in the absence of drug. 4 The calciuretic, diuretic and natriuretic activities of diltiazem and nitrendipine were not dependent on renal nerves and probably represented a direct action on the tubular reabsorptive processes of these ions. The renal nerve-induced increases in tubular calcium and sodium reabsorption indicate that these alpha-adrenoceptor-mediated responses are not dependent on the inward movement of calcium
在戊巴比妥麻醉的大鼠中,以5微克/千克·分钟的速度静脉注射地尔硫䓬,血压和肾血流量未发生变化,但肾小球滤过率增加了约16%,尿流量增加了85%,钙排泄增加了151%,钠的绝对排泄量和分数排泄量分别增加了100%和69%。在肾去神经支配的动物中也得到了类似的反应模式,只是钙排泄在统计学上没有变化。以20微克/千克·分钟的速度给肾神经完整和去神经支配的动物组注射地尔硫䓬,血压降低了15 - 17毫米汞柱,但对肾血流动力学或肾小管功能没有影响。以0.5微克/千克·分钟的速度给肾神经完整和去神经支配的动物注射尼群地平,完整动物的血压显著降低6毫米汞柱,两组的肾血流动力学均未改变,但尿流量增加了79 - 98%,钙排泄增加了87 - 125%,钠的绝对排泄量增加了108 - 140%,钠的分数排泄量增加了83 - 170%。以1.0微克/千克·分钟的速度给完整或肾去神经支配的动物输注尼群地平,血压降低了18 - 20毫米汞柱,尿流量增加了84 - 111%,钙排泄增加了85%,钠的绝对排泄量增加了81 - 137%,钠的分数排泄量增加了52 - 102%。以低频(0.8至1.5赫兹)刺激肾神经,肾血流动力学变化极小,但尿流量减少了27%,钙排泄减少了35%,钠的绝对排泄量和分数排泄量分别减少了32%和36%。在分别给予20微克/千克·分钟地尔硫䓬、0.5微克/千克·分钟或1.0微克/千克·分钟尼群地平的不同动物组中,类似程度的肾神经刺激引起的排泄反应模式与未用药时相似,且幅度相同。4地尔硫䓬和尼群地平的利钙、利尿和利钠活性不依赖于肾神经,可能代表了对这些离子肾小管重吸收过程的直接作用。肾神经引起的肾小管钙和钠重吸收增加表明,这些α - 肾上腺素能受体介导的反应不依赖于钙的内流