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Role of mineralocorticoid receptors in arterial stiffness in human aging
Moon-Hyon Hwang1, Jeung-Ki Yoo, Meredith Luttrell
1Department of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL 32611-8205, USA.
Abstract:
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 mm(2)/mmHg, 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.
Insights
Short-term mineralocorticoid receptor (MR) blockade did not reduce oxidative stress or improve arterial stiffness in older adults. These findings suggest MR do not significantly contribute to aging-related oxidative stress or arterial stiffness.
Area of Science:
- Cardiovascular Medicine
- Aging Research
- Pharmacology
Background:
- Arterial stiffness increases with age and predicts cardiovascular disease.
- Mineralocorticoid receptors (MR) are implicated in oxidative stress and arterial stiffness.
- Mechanisms underlying age-related arterial stiffness require further elucidation.
Purpose of the Study:
- To investigate whether short-term MR blockade with Eplerenone reduces oxidative stress and improves arterial stiffness in healthy older adults.
- To test the hypothesis that MR contribute to oxidative stress and arterial stiffness in aging.
Main Methods:
- A randomized, double-blind, crossover study was conducted.
- 23 healthy older adults received either Eplerenone (selective MR blocker) or placebo.
- Measurements included blood pressure, oxidative stress markers (oxidized LDL), and various arterial stiffness indices (PWV, compliance, distensibility, stiffness index, augmentation index).
Main Results:
- Brachial and carotid blood pressure decreased significantly with MR blockade (P≤0.01).
- MR blockade showed no significant effect on oxidative stress markers (oxidized LDL).
- Arterial stiffness parameters, including aortic, leg, and arm pulse wave velocity, carotid artery compliance, distensibility, β stiffness index, and augmentation index, remained unchanged.
Conclusions:
- Short-term MR blockade does not reduce oxidative stress in healthy aging individuals.
- MR blockade does not improve arterial stiffness in this population.
- These results suggest MR do not significantly contribute to oxidative stress and arterial stiffness in human aging.
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