title: Acute effect of mineralocorticoid receptor antagonism on vascular function in healthy older adults.
abstract: Mineralocorticoid receptor (MR) activation by aldosterone may regulate vascular function in health or contribute to vascular dysfunction in cardiovascular disease. Whether the effects are beneficial or detrimental to vascular function appear to be dependent on the integrity of the vascular endothelium and whether the responses are short-term or chronic. Acute modulation of MR activation has resulted in conflicting outcomes on vascular function in young healthy adults. Little is known about the vascular role of aldosterone and MR activation in healthy human aging. The primary objective of this study was to examine whether acute inhibition of MR by the selective antagonist eplerenone, influences vascular function in healthy older adults. We performed a randomized, double-blind, placebo-controlled crossover study in 22 adults (61±1 years; mean±SE, 53-79 years) who were free from overt clinical cardiovascular disease. We measured brachial artery flow-mediated endothelium-dependent dilation and endothelium-independent dilation to sublingual nitroglycerin (0.4 mg) following eplerenone (100 mg/dose, 2 doses, 24h between doses) or placebo. In response to acute MR antagonism, flow-mediated dilation decreased by 19% (from 6.9±0.5 to 5.6±0.6%, P=0.02; placebo vs. eplerenone). Endothelial nitric oxide synthase (eNOS) activity also decreased following MR antagonism based on the ratio of phosphorylated eNOS(Ser1177) to total eNOS (1.53±0.08 vs. 1.29±0.06, P=0.02). Nitroglycerin-induced dilation and blood pressure were unaffected (nitroglycerin-induced dilation: 21.9±1.9 vs. 21.0±1.5%, P=0.5 and systolic/diastolic blood pressure: 135/77±4/2 vs. 134/77±4/2 mmHg, P≥0.6). In conclusion, acute MR antagonism impairs vascular endothelial function in healthy older adults without influencing vascular smooth muscle responsiveness to exogenous nitric oxide or blood pressure.
authors.affiliation: Dept of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL, United States; Division of Health and Exercise Science, Incheon National University, Incheon, Korea.
authors.forename: Moon-Hyon
authors.initials: MH
authors.lastname: Hwang
authors.affiliation: Dept of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL, United States.
authors.forename: Jeung-Ki
authors.initials: JK
authors.lastname: Yoo
authors.affiliation: Dept of Human Physiology, University of Oregon, Eugene, OR, United States.
authors.forename: Meredith
authors.initials: M
authors.lastname: Luttrell
authors.affiliation: Dept of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL, United States.
authors.forename: Han-Kyul
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Dept of Cardiology, Baylor Scott & White Health, College Station, TX, United States; Texas A&M University Health Science Center, Bryan, TX, United States.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Meade
authors.affiliation: Dept of Family & Community Medicine, Baylor Scott & White Health, College Station, TX, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: English
authors.affiliation: Dept of Nutrition and Food Science and Dept of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, United States.
authors.forename: Susanne
authors.initials: S
authors.lastname: Talcott
authors.affiliation: Molecular Cardiology Research Institute and Division of Cardiology, Department of Medicine, Tufts Medical Center, Boston, MA, United States.
authors.forename: Iris Z
authors.initials: IZ
authors.lastname: Jaffe
authors.affiliation: Dept of Applied Physiology & Kinesiology, University of Florida, Gainesville, FL, United States. Electronic address: ddchristou@ufl.edu.
authors.forename: Demetra D
authors.initials: DD
authors.lastname: Christou
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism; D001916:Brachial Artery / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000077545:Eplerenone; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D018161:Receptors, Mineralocorticoid / Q000502:physiology; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000077545:Eplerenone
keywords: Aging; Eplerenone; Mineralocorticoid receptor; Vascular function