３．ミネラルコルチコイド受容体拮抗薬

抄録

Heart failure is currently the leading cause of death and disability across the globe. Although significant advances in pharmacological and mechanical treatments have improved the outcome of patients with heart failure, the prognosis in such patients remains poor. At present, the optimal pharmacological treatment of heart failure targets the suppression of neurohumoral activations such as the renin-angiotensin-aldosterone system (RAAS) and/or β-adrenergic receptor signaling, as well as regulation of hemodynamics. Large clinical trials in patients with heart failure, even in those with mild symptoms, have shown that mineralocorticoid receptor (MR) antagonists used in conjunction with the current standard of care improve morbidity and mortality. Increasing evidence supports the detrimental effects of aldosterone on the cardiovascular system, mainly via its MR-dependent action, in a variety of experimental models and clinical research. Of note, these unfavorable effects are more pronounced under high sodium or glucose conditions, as we and others have reported. Moreover, the pathological significance of not only systemic but also local RAAS has attracted growing attention. Furthermore, some reports have demonstrated that MR signaling can be activated without specific ligands such as aldosterone and corticosterone. Taken together, MR signaling cascades, in their high salt and/or glucose sensitive manner, play a pivotal role in the pathogenesis of heart failure. Therefore, the usefulness of MR antagonists and their indication should be more enhanced and extended, while diet control including salt restriction remains of paramount importance in the treatment of heart failure. (Jpn J Clin Pharmacol Ther 2012; 43(5): 317-322)