Role of mineralocorticoid receptors in arterial stiffness in human aging

Exp Gerontol. 2013 Aug;48(8):701-4. doi: 10.1016/j.exger.2013.05.058. Epub 2013 May 23.

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.

Keywords: Aging; Arterial stiffness; Augmentation index; Compliance; Oxidative stress; Pulse wave velocity.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / physiology*
  • Blood Pressure / drug effects
  • Blood Pressure / physiology
  • Cross-Over Studies
  • Double-Blind Method
  • Eplerenone
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / pharmacology
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • Receptors, Mineralocorticoid / drug effects
  • Receptors, Mineralocorticoid / physiology*
  • Spironolactone / analogs & derivatives
  • Spironolactone / pharmacology
  • Vascular Stiffness / physiology*

Substances

  • Mineralocorticoid Receptor Antagonists
  • Receptors, Mineralocorticoid
  • Spironolactone
  • Eplerenone