Abstract

Arterial stiffness, an independent predictor of cardiovascular disease, is increased in aging, but the underlying mechanisms are not completely understood. We hypothesized that mineralocorticoid receptor (MR) activation is partly responsible for increased arterial stiffness and that MR blockade would lead to arterial destiffening in healthy older adults. To test this hypothesis, we administered in a randomized, double blind, crossover study, 100 mg of Eplerenone (MR blocker) or placebo once per day for one month with one month washout, in 23 healthy older adults (age, 64±1 years; mean±SE) and assessed arterial stiffness (aortic, arm and leg pulse wave velocity (PWV; doppler flowmeter) and carotid artery compliance, distensibility, beta-stiffness index, augmentation index (high resolution ultrasonography and applanation tonometry). Despite reductions in blood pressure in response to Eplerenone (systolic blood pressure: 127±3 vs. 120±2 mmHg, P=0.01; diastolic blood pressure: 74±1 vs.72±1 mmHg, P=0.02; placebo vs. Eplerenone), arterial stiffness did not change (aortic PWV, 9.2±1.2 vs. 8.9±1.2m/sec, P=0.5; arm PWV, 11.4±0.6 vs. 11.7±0.7 m/sec, P=0.7; leg PWV, 13.4±0.4 vs.12.8±0.5 m/sec, P=0.3; carotid artery compliance, 0.17±0.02 vs. 0.16±0.02 mm 2 /mmHg, P=0.6; distensibility, 12.7±1.6 vs.13.6±1.5 10 -3 kPa -1 , P=0.6; beta stiffness index, 3.2±0.3 vs. 3.4±0.3, P=0.5; augmentation index, 24.3±2.9 vs. 22.0±2.9 %, P=0.3, placebo vs. Eplerenone). In conclusion, MR blockade does not result in arterial destiffening in healthy older adults despite reductions in blood pressure.

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