Role of mineralocorticoid receptors in arterial stiffness in human aging

• Arterial stiffness (AS) is increased with aging but the underlying mechanisms are unclear.
• Mineralocorticoid receptors (MR) may contribute to oxidative stress and AS.
• We performed a randomized, double blind, crossover, MR blockade study in older adults.
• Oxidative stress and AS are not improved with MR blockade in healthy human aging.

Arterial stiffness, an independent predictor of cardiovascular disease, is increased in aging, but the underlying mechanisms are not completely understood. Mineralocorticoid receptors (MR) may contribute to oxidative stress and arterial stiffness in healthy older adults. To test the hypothesis that short-term MR blockade may reduce oxidative stress and improve arterial stiffness, we conducted a randomized, double blind, crossover study using the selective MR blocker Eplerenone or placebo in 23 older adults (age, 64 ± 1 years; mean ± SE) free from overt cardiovascular and other clinical disease (e.g, diabetes, renal and liver disease). In response to MR blockade, brachial and carotid blood pressure decreased (P ≤ 0.01). However, MR blockade had no effect on oxidative stress (oxidized LDL, 61.2 ± 6.8 vs. 62.4 ± 7.4 U/L, P = 0.9; placebo vs. Eplerenone) and arterial stiffness (aortic pulse wave velocity (PWV), 9.17 ± 1.19 vs. 8.92 ± 1.19 m/s, P = 0.5; leg PWV, 13.45 ± 0.45 vs. 12.81 ± 0.47 m/s, P = 0.3; arm PWV, 11.43 ± 0.62 vs. 11.73 ± 0.68 m/s, P = 0.7; carotid artery compliance, 0.150 ± 0.013 vs. 0.149 ± 0.014 mm2/mm Hg, P = 0.8; distensibility, 23.1 ± 1.8 vs. 23.3 ± 1.7 10− 3/kPa, P = 0.8; β stiffness index, 3.5 ± 0.3 vs. 3.6 ± 0.3, P = 0.6; and augmentation index, 16.0 ± 2.2 vs. 15.6 ± 2.8%, P = 0.8). These results provide the first evidence that MR do not appear to contribute to oxidative stress in human aging and that short-term MR blockade does not result in reduced oxidative stress and improved arterial stiffness.