Gross V, Luft F C
Franz Volhard Clinic, Humboldt University of Berlin, Germany.
J Hypertens. 1996 Apr;14(4):529-35.
The mechanism by which antihypertensive drugs influence pressure natriuresis gives insight into their mode of action. We tested the effects of nisoldipine on pressure natriuresis, glomerular filtration rate, and renal blood flow in transgenic (mRen2)27 rats and Sprague-Dawley Hannover control rats.
The rats were anaesthetized, uninephrectomized with denervation of the remaining kidney, administered noradrenaline, 17-hydroxycorticosterone, vasopressin, and aldosterone to 'clamp' these regulatory systems and nisoldipine (0.5 mg/kg bolus plus 0.017 mg/kg per min). The glomerular filtration rate and renal plasma flow were measured with inulin and PAH. Renal perfusion pressure was varied from approximately 100 to approximately 200 mmHg with clamps above and below the kidney.
Nisoldipine shifted not only the pressure-diuresis and pressure-natriuresis curves but also the fractional sodium and water curves leftwards in transgenic (mRen2)27 rats, but not in Sprague-Dawley Hannover rats. Nisoldipine increased the glomerular filtration rate and renal blood flow in transgenic (mRen2)27 rats but not in Sprague-Dawley Hannover rats.
Nisoldipine shifts the pressure-natriuresis curve in transgenic (mRen2)27 rats leftwards; sodium and water excretion is increased for any given perfusion pressure. This effect is intrinsic to the kidney and is associated with inhibition of tubular sodium and water reabsorption and with an increase in renal perfusion.
抗高血压药物影响压力性利钠作用的机制有助于深入了解其作用方式。我们测试了尼索地平对转基因（mRen2）27大鼠和斯普拉格-道利汉诺威对照大鼠的压力性利钠作用、肾小球滤过率和肾血流量的影响。
将大鼠麻醉，切除一侧肾脏并对剩余肾脏去神经支配，给予去甲肾上腺素、17-羟皮质酮、血管加压素和醛固酮以“钳制”这些调节系统，然后给予尼索地平（0.5mg/kg推注加0.017mg/kg每分钟）。用菊粉和对氨基马尿酸测量肾小球滤过率和肾血浆流量。通过在肾脏上方和下方使用夹子将肾灌注压在约100至约200mmHg之间变化。
尼索地平不仅使转基因（mRen2）27大鼠的压力-利尿和压力-利钠曲线向左移动，还使钠和水分数曲线向左移动，但在斯普拉格-道利汉诺威大鼠中未出现这种情况。尼索地平增加了转基因（mRen2）27大鼠的肾小球滤过率和肾血流量，但在斯普拉格-道利汉诺威大鼠中未增加。
尼索地平使转基因（mRen2）27大鼠的压力-利钠曲线向左移动；在任何给定的灌注压力下，钠和水的排泄都会增加。这种作用是肾脏固有的，与肾小管对钠和水重吸收的抑制以及肾灌注的增加有关。
