Upregulated Renal Mineralocorticoid Receptor and 11β-Hydroxysteroid Dehydrogenase Type 2 Are Associated with K(+) Retention During MR Antagonism in Female Spontaneously Hypertensive Rats.
I, B., I, B., S, A., B, T., A, C., V, B., M, F., C, G.S., & M, M. (2026). Upregulated Renal Mineralocorticoid Receptor and 11β-Hydroxysteroid Dehydrogenase Type 2 Are Associated with K(+) Retention During MR Antagonism in Female Spontaneously Hypertensive Rats.. International journal of molecular sciences. https://doi.org/10.3390/ijms27156953
I B, I B, S A, B T, A C, V B, et al. Upregulated Renal Mineralocorticoid Receptor and 11β-Hydroxysteroid Dehydrogenase Type 2 Are Associated with K(+) Retention During MR Antagonism in Female Spontaneously Hypertensive Rats.. International journal of molecular sciences. 2026; doi: 10.3390/ijms27156953
I B, I B, S A, et al. Upregulated Renal Mineralocorticoid Receptor and 11β-Hydroxysteroid Dehydrogenase Type 2 Are Associated with K(+) Retention During MR Antagonism in Female Spontaneously Hypertensive Rats.[J]. International journal of molecular sciences. 2026. DOI: 10.3390/ijms27156953.
@article{i2026,
author = {Baranovskaya I and Bilous I and Alexander S and Tubalinal B and Cherezova A and Buncha V and Fomin M and Gomez-Sanchez C and Mamenko M},
title = {Upregulated Renal Mineralocorticoid Receptor and 11β-Hydroxysteroid Dehydrogenase Type 2 Are Associated with K(+) Retention During MR Antagonism in Female Spontaneously Hypertensive Rats.},
journal = {International journal of molecular sciences},
year = {2026},
doi = {10.3390/ijms27156953},
note = {PMID: 42589607},
}
TY - JOUR AU - Baranovskaya I AU - Bilous I AU - Alexander S AU - Tubalinal B AU - Cherezova A AU - Buncha V AU - Fomin M AU - Gomez-Sanchez C AU - Mamenko M TI - Upregulated Renal Mineralocorticoid Receptor and 11β-Hydroxysteroid Dehydrogenase Type 2 Are Associated with K(+) Retention During MR Antagonism in Female Spontaneously Hypertensive Rats. T2 - International journal of molecular sciences PY - 2026 DO - 10.3390/ijms27156953 AN - PMID:42589607 ER -
Mineralocorticoid receptor (MR) blockade exerts sex-specific effects in hypertension and cardiovascular disease; however, its role in blood pressure regulation in spontaneously hypertensive rats (SHRs) remains unclear. We assessed the effects of MR antagonism on blood pressure and electrolyte balance in male and female SHRs aged 10-15 weeks. Higher serum K+ levels in spironolactone-treated female SHRs were accompanied by transiently reduced urinary K+ excretion and a fourfold increase in aldosterone at the study's end. These differences were not observed in male SHRs. Plasma renin activity and circulating corticosterone were 19% and 41% lower in females than in males but were unaffected by spironolactone in either sex. Plasma renin activity in SHRs was comparable to that of normotensive Wistar-Kyoto rats. Females exhibited approximately twofold higher renal MR and 1.7-fold greater renal 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) protein levels. MR antagonism did not alter ENaC activity, α-ENaC protein abundance, blood pressure, or amiloride-sensitive urinary electrolyte excretion in either sex. Collectively, the upregulation of renal MR and 11β-HSD2 in females was associated with elevated circulating potassium in response to MR blockade, an effect that was likely counterbalanced by a compensatory rise in aldosterone. Low renin-angiotensin-aldosterone system activity in SHRs may limit the antihypertensive efficacy of MR antagonists.