Neumayer H H, Kunzendorf U
Department of Internal Medicine and Nephrology, University of Erlangen-Nürnberg, Germany.
J Cardiovasc Pharmacol. 1991;18 Suppl 1:S11-8.
In addition to their role as highly potent antihypertensive drugs, calcium antagonists may also play an important future role in the area of tissue protection and preservation. Calcium antagonists exert favorable effects on renal hemodynamics related to their reversal of renal vasoconstrictors. Calcium antagonists are also capable of blocking intracellular calcium overload induced by various types of ischemic or toxic stimuli. Features such as these may be of substantial value in ameliorating acute renal insufficiency secondary to renal ischemia, iodinated radiographic contrast agents, or the administration of various nephrotoxic drugs. The latter includes agents such as the aminoglycoside antibiotics, cyclosporine A, and the cancer chemotherapeutic agent cisplatin. Recent prospective, controlled studies from our group indicate that calcium antagonists protected against postischemic acute renal failure in the setting of cadaveric renal transplantation. Moreover, in a prospective, randomized, controlled clinical trial, we were able to demonstrate that the prophylactic use of nitrendipine reduced the decrease in GFR in patients receiving radiographic contrast agents. Calcium antagonists may also play a beneficial role in preventing progressive renal disease. Data from a number of studies conducted in experimental animals, as well as information from clinical trials, support such a view. Although the mechanisms of action of calcium antagonists in the setting of chronic renal failure are not yet fully established, their beneficial effects may be related to protective actions such as the reduction in renal hypertrophy, modulation of mesangial cell uptake of macromolecules, changes in permselectivity of the glomerulus, and a decreased free radical formation. These various aspects will be the topic in this review.
除了作为高效的抗高血压药物发挥作用外，钙拮抗剂在组织保护和保存领域未来可能也会发挥重要作用。钙拮抗剂对肾血流动力学具有有利影响，这与其逆转肾血管收缩剂有关。钙拮抗剂还能够阻断由各种类型的缺血或毒性刺激所诱导的细胞内钙超载。诸如此类特性在改善继发于肾缺血、碘化造影剂或各种肾毒性药物给药后的急性肾功能不全方面可能具有重大价值。后者包括氨基糖苷类抗生素、环孢素A以及癌症化疗药物顺铂等药物。我们团队最近的前瞻性对照研究表明，钙拮抗剂可预防尸体肾移植中缺血后急性肾衰竭。此外，在一项前瞻性、随机、对照临床试验中，我们能够证明预防性使用尼群地平可减少接受造影剂患者的肾小球滤过率下降。钙拮抗剂在预防进行性肾病方面可能也发挥有益作用。在实验动物中进行的多项研究数据以及临床试验信息均支持这一观点。尽管钙拮抗剂在慢性肾衰竭情况下的作用机制尚未完全明确，但其有益作用可能与诸如减轻肾肥大、调节系膜细胞对大分子的摄取、改变肾小球的选择通透性以及减少自由基形成等保护作用有关。这些不同方面将是本综述的主题。
