CARDIOVASCULAR AND RENAL ACTIONS OF CALCIUM-CHANNEL BLOCKER CHEMICAL SUBGROUPS - A SEARCH FOR RENAL SPECIFICITY
CARDIOVASCULAR AND RENAL ACTIONS OF CALCIUM-CHANNEL BLOCKER CHEMICAL SUBGROUPS - A SEARCH FOR RENAL SPECIFICITY
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DOI：
10.1111/j.2042-7158.1988.tb06305.x
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发表时间：
1988-06-01
影响因子：
3.3
通讯作者：
PROAKIS, AG
中科院分区：
文献类型：
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作者：
BARRETT, RJ;WRIGHT, KF;PROAKIS, AG
利尿剂和利钠反应的结构不同类别的钙通道阻滞剂进行了比较，以确定是否有任何代理人引起的K+-保留尿钠排泄，并评估这种反应与药物对血压的影响的关系。清醒血压正常的Sprague-Dawley大鼠接受溶剂或以下药物之一的口服生理盐水负荷（40 mL kg-1）：硝苯地平，尼莫地平，尼群地平，戊烯胺，桂利嗪，氟桂利嗪，地尔硫卓，维拉帕米，氢氯噻嗪，阿米洛利，或肼苯哒嗪，剂量为0.316至100 mg kg-1。收集尿液6 h。在平行研究中直接监测血压。尽管存在明显的低血压，地尔硫卓（31.6，100 mg kg-1）和氟桂利嗪（100 mg kg-1）仍能增加尿液和电解质排泄;地尔硫卓是唯一产生剂量相关肾脏反应的药物。相反，肼苯哒嗪和硝苯地平的等效剂量产生明显的尿液和电解质潴留。尼群地平和戊烯胺（0.316毫克公斤-1）产生轻微的利尿或尿钠排泄，而不改变血压;更高的剂量没有影响。维拉帕米、尼群地平和尼莫地平的31.6 mg kg-1剂量显著降低血压，但既不增强也不限制尿和电解质排泄。桂利嗪未产生任何心血管或肾脏效应。由Ca 2+通道阻滞剂引起的利尿反应没有类别特异性，没有显示出保留K+的趋势，通常弱于低剂量阿米洛利或氢氯噻嗪产生的反应，并且与药物引起的血压变化无关。
The diuretic and natriuretic responses to structurally distinct classes of Ca2+ channel blockers have been compared, to determine whether any agent provoked K+-sparing natriuresis, and to assess the relation of such responses with drug effects on blood pressure. Conscious normotensive Sprague-Dawley rats received vehicle or one of the followong drugs in an oral saline load (40 mL kg-1): nifedipine, nimodipine, nitrendipine, prenylamine, cinnarizine, flunarizine, diltiazem, verapamil, hydrochlorothiazide, amiloride, or hydralazine, at doses from 0.316 to 100 mg kg-1. Urine was collected for 6 h. Blood pressure was monitored directly in parallel studies. Diltiazem (31.6, 100 mg kg-1) and flunarizine (100 mg kg-1) enhanced urine and electrolyte excretion in spite of marked hypotension; diltiazem was the only drug to produce dose-related renal responses. In contrast, equihypotensive doses of hydralazine and nifedipine produced overt urine and electrolyte retention. Nitrendipine and prenylamine (0.316 mg kg-1 each) produced slight diuresis or natriuresis without altering blood pressure; higher doses had no effect. The 31.6 mg kg-1 doses of verapamil, nitrendipine, and nimodipine markedly reduced blood pressure, but neither enhanced nor limited urine and electrolyte excretion. Cinnarizine failed to produce any cardiovascular or renal effects. Diuretic responses evoked by the Ca2+ channel blockers were not class-specific, showed no tendency towards sparing K+, were generally weaker than those produced by low doses of amiloride or hydrochlorothiazide, and were dissociable from drug-induced changes in blood pressure.