title: Effect of Selective Mineralocorticoid Receptor Blockade on Flow-Mediated Dilation and Insulin Resistance in Older Adults with Metabolic Syndrome.
abstract: BACKGROUND
  The prevalence of metabolic syndrome is especially high in older adults. Metabolic syndrome is associated with impaired vascular endothelial function, insulin resistance, and increased risk for cardiovascular disease but the underlying mechanisms are not fully elucidated. Plasma aldosterone is independently associated with metabolic syndrome and is linked to endothelial dysfunction and insulin resistance. Thus, we hypothesized that mineralocorticoid receptor (MR) blockade would improve flow-mediated dilation and insulin resistance in older adults with metabolic syndrome.
  
  
  METHODS
  To test this hypothesis, we conducted a balanced, randomized, double-blind, placebo-controlled, crossover study using selective MR blockade (eplerenone; 100 mg/day) for 1 month with 1 month washout in older adults with metabolic syndrome (62.6 ± 3.2 yrs; mean ± standard error). We evaluated brachial artery flow-mediated dilation (ultrasonography), oxidative stress (oxidized low-density lipoproteins and F2-isoprostanes) and insulin resistance (homeostatic model assessment).
  
  
  RESULTS
  In response to MR blockade, flow-mediated dilation (5.37 ± 0.85 vs. 5.98 ± 1.29%; placebo vs. eplerenone; P = 0.4), oxidized low-density lipoproteins (51.6 ± 11.5 vs. 56.1 ± 10.9 U/L; P = 0.6), and F2-isoprostanes (0.07 ± 0.02 vs. 0.06 ± 0.01 pg/mL; P = 0.3) did not improve. Insulin resistance also did not change following MR blockade (1.04 ± 0.26 vs. 1.38 ± 0.50; P = 0.6). However, MR blockade resulted in a large reduction (10 mmHg) in systolic blood pressure (140 ± 6 vs. 130 ± 6 mmHg; P = 0.02), with no significant change in diastolic blood pressure (81 ± 3 vs. 75 ± 2 mmHg; P = 0.2).
  
  
  CONCLUSIONS
  Our data do not support a contributing role for MRs in endothelial dysfunction and insulin resistance in older adults with metabolic syndrome. However, our findings suggest MR activation is an important contributor to systolic hypertension in this patient group.
authors: 1 Department of Applied Physiology and Kinesiology, University of Florida , Gainesville, Florida.|2 Division of Health and Exercise Science, Incheon National University , Incheon, Korea.
authors: Moon-Hyon
authors: MH
authors: Hwang
authors: 1 Department of Applied Physiology and Kinesiology, University of Florida , Gainesville, Florida.
authors: Jeung-Ki
authors: JK
authors: Yoo
authors: 3 Department of Human Physiology, University of Oregon , Eugene, Oregon.
authors: Meredith
authors: M
authors: Luttrell
authors: 4 Department of Cardiology, Baylor Scott and White Health, Texas A&M University , College Station, Texas.
authors: Thomas H
authors: TH
authors: Meade
authors: 5 Department of Family and Community Medicine, Baylor Scott and White Health, Texas A&M University , College Station, Texas.
authors: Mark
authors: M
authors: English
authors: 1 Department of Applied Physiology and Kinesiology, University of Florida , Gainesville, Florida.
authors: Demetra D
authors: DD
authors: Christou
mesh_terms: D000368:Aged; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D000077545:Eplerenone; D006801:Humans; D007333:Insulin Resistance; D024821:Metabolic Syndrome / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D010919:Placebos; D012039:Regional Blood Flow / Q000187:drug effects* / Q000502:physiology; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D010919:Placebos; D013148:Spironolactone; D000077545:Eplerenone