Kageyama M, Matsumura Y, Sasaki Y, Ichihara T, Hosokawa T, Hayashi K, Morimoto S
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
J Cardiovasc Pharmacol. 1989 Jul;14(1):96-102. doi: 10.1097/00005344-198907000-00017.
Renal effects of nisoldipine, a potent calcium channel blocker, were examined in anesthetized dogs. Intrarenal arterial infusion of nisoldipine (2, 10, and 50 ng/kg per min) had no effect on mean systemic blood pressure and heart rate and there was no significant change in renal hemodynamics during infusion of various doses of the drug. Urine flow and urinary excretions of sodium, chloride, and potassium were increased by nisoldipine in a dose-related manner. Fractional excretions of sodium and chloride were markedly elevated with the highest dose given thereby indicating that tubular reabsorptions of sodium and chloride were inhibited by nisoldipine. Nisoldipine (50 ng/kg per min) abolished the decreasing effects of angiotensin-II on glomerular filtration rate, urine flow, and urinary excretion of electrolytes but not the decrease in renal blood flow by the peptide. Angiotensin-II-induced reduction of fractional excretion of electrolytes was completely blocked by nisoldipine. Renal responses to norepinephrine were unaffected by nisoldipine. Thus, nisoldipine administered intrarenally to anesthetized dogs exerts a diuretic action by way of tubular effects, as is the case with other dihydropyridine calcium channel blockers. Nisoldipine seems to effectively antagonize the renal response to angiotensin-II. Thus, the preferential inhibition of angiotensin-II-induced antidiuresis may mean that nisoldipine interferes with stimulatory effects of angiotensin-II on the renal tubular reabsorption of electrolytes and water.
在麻醉犬中研究了强效钙通道阻滞剂尼索地平的肾脏效应。肾内动脉输注尼索地平（每分钟2、10和50纳克/千克）对平均体循环血压和心率无影响，在输注不同剂量药物期间肾脏血流动力学也无显著变化。尼索地平以剂量相关的方式增加尿流量以及钠、氯和钾的尿排泄量。给予最高剂量时，钠和氯的排泄分数显著升高，从而表明尼索地平抑制了钠和氯的肾小管重吸收。尼索地平（每分钟50纳克/千克）消除了血管紧张素II对肾小球滤过率、尿流量和电解质尿排泄的降低作用，但未消除该肽对肾血流量的降低作用。血管紧张素II诱导的电解质排泄分数降低被尼索地平完全阻断。尼索地平不影响肾脏对去甲肾上腺素的反应。因此，对麻醉犬肾内给予尼索地平通过肾小管效应发挥利尿作用，其他二氢吡啶类钙通道阻滞剂也是如此。尼索地平似乎能有效拮抗肾脏对血管紧张素II的反应。因此，对血管紧张素II诱导的抗利尿作用的优先抑制可能意味着尼索地平干扰了血管紧张素II对肾小管电解质和水重吸收的刺激作用。
