Finerenone improves vascular function in association with reduced aortic sodium content in aldosterone/salt-loaded uninephrectomized rats.

Authors

Md Moshiur Rahman, Asadur Rahman, Masashi Tawa, Hiroyuki Ohsaki, Keisuke Nakagawa, Netish Kumar Kundo, Akram Hossain, Juanjuan Ye, Liu Changjin, Md Enayet Kabir, Daisuke Yamazaki, Takashi Morikawa, Yoshio Konishi, Mamoru Ohkita, Kento Kitada, Akira Nishiyama

Published in

Journal of pharmacological sciences. Volume 162. Issue 3. Pages 213-223. Epub Sep 08, 2026.

Abstract

Mineralocorticoid receptor (MR) overactivation and high salt intake drive vascular dysfunction, characterized by endothelial impairment and stiffening. While the novel non-steroidal MR antagonist (MRA), finerenone improves cardiovascular outcomes in patients with heart failure, its specific effects on vascular sodium accumulation remain unknown. We investigated the effects of finerenone on vascular function, remodeling, and aortic sodium content. Uninephrectomized (UNx) Sprague Dawley rats were subjected to chronic aldosterone infusion (0.75 μg/h) and salt-loading (1% NaCl in drinking water) for 4 weeks, with concurrent oral administration of finerenone (10 mg/kg). Finerenone intervention improved survival and significantly decreased systolic blood pressure. Vascular function analyses revealed that both endothelium-dependent and -independent relaxation were impaired in the model group; however, finerenone significantly preserved these functions. Importantly, sodium content in the aortic tissues as well as plasma was markedly elevated in aldosterone/salt-loaded UNx rats but was significantly reduced by finerenone, concurrent with the downregulation of the MR target gene serum glucocorticoid-regulated kinase 1 (Sgk1). In addition, finerenone attenuated vascular fibrosis and hypertrophy, and restored the aortic nitric oxide level. Altogether, these findings suggest that finerenone ameliorates vascular dysfunction by targeting MR/Sgk1-mediated vascular sodium accumulation and maladaptive remodeling, in concert with systemic blood pressure reduction.

PMID:
42810778
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.

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