van Hamersvelt H W, Wetzels J F, Koene R A, Huysmans F T
Department of Medicine, Sint Radboud Hospital, University of Nijmegen, Netherlands.
Hypertension. 1994 Nov;24(5):633-9. doi: 10.1161/01.hyp.24.5.633.
Calcium entry blockers such as felodipine induce natriuresis without a parallel rise of potassium excretion. Previous studies with exogenous aldosterone and felodipine have suggested that the absence of kaliuresis might be explained by a felodipine-induced inhibition of aldosterone release. The natriuresis with calcium entry blockers could not be attributed to a similar mechanism but might be due to the stimulation of intrarenal natriuretic systems such as the dopaminergic system. We studied whether the aselective dopamine antagonist metoclopramide prevents the natriuresis with low and therapeutic felodipine doses and whether metoclopramide-induced aldosterone release promotes kaliuresis with felodipine. Twelve healthy male volunteers participated in a randomized, placebo-controlled, crossover study comparing felodipine infusion during metoclopramide with felodipine alone. Metoclopramide had no significant influence on the pronounced and dose-dependent increases of renal plasma flow and urinary sodium excretion with felodipine. Metoclopramide increased plasma aldosterone concentration from 0.17 +/- 0.03 to 0.60 +/- 0.14 nmol/L, and subsequent felodipine infusion clearly increased urinary potassium excretion by 23 +/- 6 and 35 +/- 8 mumol/min (low and therapeutic doses, respectively). In contrast, potassium excretion remained stable with felodipine alone (+5 +/- 4 and +7 +/- 5 mumol/min, respectively). In conclusion, the natriuretic action of calcium entry blockers cannot be blocked by the aselective dopamine antagonist metoclopramide. This natriuresis is accompanied by kaliuresis only in the presence of elevated endogenous aldosterone concentrations. The ability of calcium entry blockers to prevent a rise of plasma aldosterone thus seems essential for the prevention of urinary potassium losses.
像非洛地平这样的钙通道阻滞剂可诱导利钠作用，而钾排泄量却没有相应增加。先前使用外源性醛固酮和非洛地平的研究表明，无尿钾增多现象可能是由于非洛地平抑制了醛固酮释放。钙通道阻滞剂的利钠作用并非归因于类似机制，而可能是由于刺激了肾内利钠系统，如多巴胺能系统。我们研究了非选择性多巴胺拮抗剂甲氧氯普胺是否能阻止低剂量和治疗剂量非洛地平的利钠作用，以及甲氧氯普胺诱导的醛固酮释放是否能促进非洛地平的尿钾增多。12名健康男性志愿者参与了一项随机、安慰剂对照、交叉研究，比较了甲氧氯普胺输注期间非洛地平与单独使用非洛地平的情况。甲氧氯普胺对非洛地平引起的肾血浆流量和尿钠排泄的显著且剂量依赖性增加没有显著影响。甲氧氯普胺使血浆醛固酮浓度从0.17±0.03纳摩尔/升增加到0.60±0.14纳摩尔/升，随后输注非洛地平明显使尿钾排泄量分别增加23±6和35±8微摩尔/分钟（低剂量和治疗剂量）。相比之下，单独使用非洛地平时钾排泄量保持稳定（分别为+5±4和+7±5微摩尔/分钟）。总之，非选择性多巴胺拮抗剂甲氧氯普胺不能阻断钙通道阻滞剂的利钠作用。只有在内源性醛固酮浓度升高时，这种利钠作用才会伴有尿钾增多。因此，钙通道阻滞剂预防血浆醛固酮升高的能力似乎对防止尿钾流失至关重要。
