Finerenone treatment for 4 weeks significantly lowered the β-index of intrinsic arterial stiffness in MWF rats compared to vehicle (7.7 vs. 9.2, p < 0.05).
Does finerenone reduce intrinsic arterial stiffness in a rat model of chronic kidney disease?
In a rat model of chronic kidney disease, finerenone reduced intrinsic arterial stiffness, which correlated with reductions in albuminuria and improvements in endothelial function.
Absolute Event Rate: 7.7% vs 9.2%
p-value: p=<0.05
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.
Gil‐Ortega et al. (Wed,) conducted a other in Chronic kidney disease (animal model). Finerenone vs. Vehicle was evaluated on Intrinsic arterial stiffness (β-index) in mesenteric arteries (p=<0.05). Finerenone treatment for 4 weeks significantly lowered the β-index of intrinsic arterial stiffness in MWF rats compared to vehicle (7.7 vs. 9.2, p < 0.05).