Abstract
Background: There is accumulating evidence that increased levels of aldosterone (Aldo) and increased vascular mineralocorticoid receptor (MR) signaling increases vascular inflammation and oxidative stress leading to endothelial dysfunction and associated vascular stiffness. However, the specific role of endothelial cell (EC) MR activation in promotion of end stiffness in female mice has not been explored. Accordingly, we hypothesized that knocking out MR from ECs would attenuate the Aldo-induced endothelial dysfunction and vascular stiffness. Methods and Results: Twenty six week-old female ECMR knockout (ECMR-/-) and wild type (ECMR+/+) mice were infused with 250 μg/Kg/day Aldo for 3 weeks. To assess endothelial-dependent vasodilation, endothelial and aortic stiffness and blood pressure we utilized wire myography, atomic force microscopy (AFM), pulse wave velocity (PWV) (before and after Aldo perfusion) and tail cuff procedures. Aldo infusion did not increase BP or PWV and this was not affected by the presence or absence of ECMR. Aldo impaired endothelial-dependent vasodilation and increased EC stiffness 8.6 fold and these effects were mitigated in ECMR-/-. Aldo did not alter peri-aortic fibrosis by picrosirius red staining as measured by average gray scale intensities, nor did it cause medial thickening or aortic remodeling evaluated by the lumen to aortic wall ratio, in either Aldo-infused group. Moreover, levels of the oxidative marker, 3-nitrotyrosine (3-NT) did not differ in different compartments of the aortic wall in either Aldo treated group. Conclusion: ECMR protects the endothelium from aldo-mediated impaired vasodilation and endothelial cell stiffness, and this protection occurs without changes in BP, total aortic stiffness, or vascular remodeling.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call