Namsolleck Pawel, Unger Thomas
CARIM-School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.
Nephrol Dial Transplant. 2014 Feb;29 Suppl 1:i62-i68. doi: 10.1093/ndt/gft402.
Aldosterone is involved in various cardiovascular pathologies, including hypertension, heart failure, atherosclerosis and fibrosis. Mineralocorticoid receptor (MR)-dependent and -independent, genomic and non-genomic processes mediate its complex effects. Spironolactone and eplerenone, both MR antagonists, are the only commercially available compounds targeting directly the actions of aldosterone. However, due to the poor selectivity (spironolactone), low potency (eplerenone) and the fact that only MR-dependent effects of aldosterone can be inhibited, these drugs have limited clinical use. An attractive approach to abolish potentially all of aldosterone-mediated pathologies is the inhibition of aldosterone synthase. This review summarizes current knowledge on the complex effects mediated by aldosterone, potential advantages and disadvantages of aldosterone inhibition and novel directions in the development of aldosterone synthase inhibitors.
醛固酮参与多种心血管疾病，包括高血压、心力衰竭、动脉粥样硬化和纤维化。盐皮质激素受体（MR）依赖性和非依赖性的基因组和非基因组过程介导其复杂作用。螺内酯和依普利酮均为MR拮抗剂，是仅有的可直接针对醛固酮作用的市售化合物。然而，由于选择性差（螺内酯）、效力低（依普利酮）以及只能抑制醛固酮的MR依赖性作用这一事实，这些药物的临床应用有限。抑制醛固酮合酶是一种有望消除所有潜在的醛固酮介导疾病的方法。本综述总结了目前关于醛固酮介导的复杂作用、醛固酮抑制的潜在优缺点以及醛固酮合酶抑制剂开发新方向的知识。
