Short‐ and long‐term administration of the non‐steroidal mineralocorticoid receptor antagonist finerenone opposes metabolic syndrome‐related cardio‐renal dysfunction

Abstract

In rats with metabolic syndrome, the non-steroidal MR antagonist finerenone opposed metabolic syndrome-related diastolic cardiac dysfunction and nephropathy. This involved acute effects, such as improved myocardial perfusion, reduced oxidative stress/increased NO bioavailability, as well as long-term effects, such as modifications in the myocardial structure.

Mineralocorticoid receptor antagonists and kidney diseases: pathophysiological basis

“…87 In the Zucker-obese rat, finerenone reduced proteinuria and renal NGAL expression. 88 In a severe model that combines obesity, hypertension, and high salt (spontaneously hypertensive [SHR]/cps rat), massive proteinuria, severe renal lesions, and podocyte injury were observed; eplerenone dramatically ameliorated proteinuria and renal injury in these animals. 89 Mice with obesity induced by a high-fat diet develop kidney injury, characterized by glomerular hypercellularity, mesangium expansion, albuminuria, and increased rho kinase activity; all of these alterations were attenuated by eplerenone.…”

Vascular and inflammatory mineralocorticoid receptors in kidney disease

“…36,49,58 A benefit of MR inhibition has also been described in rodent models of diabetic kidney disease. 64 In female mice, in which obesity was induced by a western diet, the deletion of the MR in ECs prevented proteinuria, inflammation, kidney fibrosis and renal endothelial stiffness. [59][60][61] Similarly, MR antagonism reduced albuminuria, mesangial expansion and fibrosis in type 2 diabetic db/db mice.…”

“…63 In the Zucker rat, a model of metabolic syndrome, MR blockade with finerenone prevented cardiac dysfunction, oxidative injury and cardiac remodelling. 64 In female mice, in which obesity was induced by a western diet, the deletion of the MR in ECs prevented proteinuria, inflammation, kidney fibrosis and renal endothelial stiffness. 65 These mice also showed lower eNOS activation, together with greater oxidative injury and NOX2 expression.…”

Potential Benefit of Mineralocorticoid Receptor Antagonists in Kidney Diseases

“…The novel nonsteroidal MRA AZ9977 has similar effects [63]. In the Otsuka Long-Evans Tokushima Fatty (OLETF) rats or Zucker obese rats, similar benefits have been reported after MRA treatment [64,65].…”