盐皮质激素受体
医学
脑利钠肽
螺内酯
肾脏疾病
心钠素
药理学
依普利酮
内分泌学
心脏病学
醛固酮
内科学
心力衰竭
作者
Peter Kolkhof,Martina Delbeck,Axel Kretschmer,Wolfram Steinke,Elke Hartmann,Lars Bärfacker,Frank Eitner,Barbara Albrecht-Küpper,Stefan Schäfer
出处
期刊:Journal of Cardiovascular Pharmacology
[Ovid Technologies (Wolters Kluwer)]
日期:2014-07-01
卷期号:64 (1): 69-78
被引量:263
标识
DOI:10.1097/fjc.0000000000000091
摘要
Pharmacological blockade of the mineralocorticoid receptor (MR) ameliorates end-organ damage in chronic heart failure. However, the clinical use of available steroidal MR antagonists is restricted because of concomitant hyperkalemia especially in patients with diminished kidney function. We have recently identified a novel nonsteroidal MR antagonist, finerenone, which uniquely combines potency and selectivity toward MR. Here, we investigated the tissue distribution and chronic cardiorenal end-organ protection of finerenone in comparison to the steroidal MR antagonist, eplerenone, in 2 different preclinical rat disease models. Quantitative whole-body autoradiography revealed that [14C]-labeled finerenone equally distributes into rat cardiac and renal tissues. Finerenone treatment prevented deoxycorticosterone acetate-/salt-challenged rats from functional as well as structural heart and kidney damage at dosages not reducing systemic blood pressure. Finerenone reduced cardiac hypertrophy, plasma prohormone of brain natriuretic peptide, and proteinuria more efficiently than eplerenone when comparing equinatriuretic doses. In rats that developed chronic heart failure after coronary artery ligation, finerenone (1 mg·kg−1·d−1), but not eplerenone (100 mg·kg−1·d−1) improved systolic and diastolic left ventricular function and reduced plasma prohormone of brain natriuretic peptide levels. We conclude that finerenone may offer end-organ protection with a reduced risk of electrolyte disturbances.
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