Osswald H, Weinheimer G, Kapp J F
Gödecke Research Institute, Freiburg, Federal Republic of Germany.
J Neural Transm Suppl. 1990;31:39-53.
The actions of L-channel calcium antagonists on the kidney are the result of direct and indirect effects. The direct effects are characterized by vasodilation, especially when the renal vascular resistance was enhanced beforehand. The increase in glomerular filtration rate is small and transient in most of the clinical trials with chronic administration. An important direct effect of calcium channel antagonists on renal function is the increase of sodium and water excretion by a tubular action that occurs in the absence of hemodynamic changes. The mechanism of the tubular effects of calcium channel antagonists is not understood at present. An indirect effect of calcium channel antagonists on the kidney is the inhibition of the aldosterone secretion by the adrenals. A sodium and water loss due to inhibition of tubular reabsorption leads to an increase in renin activity and aldosterone concentration in the plasma as seen typically with diuretics. The dissociation of renin- and aldosterone increase by calcium channel antagonists is a new finding and contributes favorably to the anti-hypertensive efficacy of calcium channel antagonists. In experimental acute renal failure mainly diltiazem and verapamil improved recovery of kidney function. In kidney transplantation, diltiazem reduced posttransplant acute tubular necrosis and improved primary graft function. It remains to be seen whether other calcium channel antagonists have a similar beneficial therapeutic effect in pathological states of renal function.
L型钙通道拮抗剂对肾脏的作用是直接和间接作用的结果。直接作用的特点是血管舒张，尤其是在肾血管阻力预先增加的情况下。在大多数长期给药的临床试验中，肾小球滤过率的增加很小且是短暂的。钙通道拮抗剂对肾功能的一个重要直接作用是通过在无血流动力学变化时发生的肾小管作用增加钠和水的排泄。目前尚不清楚钙通道拮抗剂肾小管作用的机制。钙通道拮抗剂对肾脏的间接作用是抑制肾上腺醛固酮的分泌。与利尿剂通常所见情况一样，由于肾小管重吸收受抑制导致的钠和水丢失会导致血浆肾素活性和醛固酮浓度增加。钙通道拮抗剂使肾素和醛固酮增加相分离是一项新发现，对钙通道拮抗剂的降压疗效有积极作用。在实验性急性肾衰竭中，主要是地尔硫䓬和维拉帕米改善了肾功能的恢复。在肾脏移植中，地尔硫䓬减少了移植后急性肾小管坏死并改善了原发性移植物功能。其他钙通道拮抗剂在肾功能病理状态下是否具有类似的有益治疗效果还有待观察。
