RT Journal Article
T1 Finerenone Reduces Intrinsic Arterial Stiffness in Munich Wistar Frömter Rats, a Genetic Model of Chronic Kidney Disease
A1 Gil-Ortega, Marta
A1 Vega-Martín, Elena
A1 Martín-Ramos, Miriam
A1 González-Blázquez, Raquel
A1 Pulido-Olmo, Helena
A1 Ruiz-Hurtado, Gema
A1 Schulz, Angela
A1 Ruilope, Luis
A1 Kolkhof, Peter
A1 Somoza, Beatriz
A1 Kreutz, Reinhold
A1 Fernández Alfonso, María Soledad
AB Background: Development of albuminuria and arterial stiffness in Munich Wistar Frömter (MWF) rats, a model of chronic kidney disease, is related to alterations in extracellular matrix, increased oxidative stress, and endothelial dysfunction. Finerenone (FIN), a novel, nonsteroidal, potent, and selective mineralocorticoid receptor antagonist, improves endothelial dysfunction through enhancing nitric oxide (NO) bioavailability and decreasing superoxide anion levels due to an upregulation in vascular and renal superoxide dismutase activity. We hypothesize that FIN reduces arterial stiffness in this model associated to the reduction in albuminuria and matrix metalloproteinase (MMP)-2/9 activity. Methods: Twelve-week-old MWF rats with established albuminuria and age-matched normoalbuminuric Wistar (W) rats were treated with FIN (10 mg/kg/day, once-daily oral gavage) or with vehicle (control, C) for 4 weeks. Results: Arterial stiffness was significantly higher in mesenteric arteries (MA) of MWF-C as compared to W-C. FIN treatment significantly lowered β-index, a measure of intrinsic stiffness independent of geometry, in MWF (βMWF-FIN = 7.7 ± 0.4 vs. βMWF-C = 9.2 ± 0.5, p < 0.05) positively correlating with urinary albumin excretion. Elastin fenestrae area in the internal elastic lamina of MA from MWF-FIN was significantly larger (+377%, p < 0.05). FIN increased plasma pro-MMP-2 and decreased plasma MMP-2 and MMP-9 activities, correlating with reductions in β-index. MA from MWF-FIN exhibited higher NO bioavailability and reduced superoxide anion levels compared to MWF-C. Conclusion: FIN treatment reduces intrinsic arterial stiffness in MA from MWF rats associated with changes in elastin organization, normalization of MMP-2 and MMP-9 activities, and reduction of oxidative stress. Moreover, reduction of arterial stiffness correlates with reduction in albuminuria.
PB Karger Publishers
SN 0250-8095
YR 2020
FD 2020
LK https://hdl.handle.net/20.500.14352/93782
UL https://hdl.handle.net/20.500.14352/93782
LA eng
NO Gil-Ortega M, Vega-Martín E, Martín-Ramos M, González-Blázquez R, Pulido-Olmo H, Ruiz-Hurtado G, et al. Finerenone Reduces Intrinsic Arterial Stiffness in Munich Wistar Frömter Rats, a Genetic Model of Chronic Kidney Disease. Am J Nephrol 2020;51:294–303. https://doi.org/10.1159/000506275.
NO Bayer Pharma AG
NO Fundación Eugenio Rodríguez Pascual
NO Sociedad para el Estudio de la Salud Cardiometabólica 
DS Docta Complutense
RD 8 abr 2025