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Acute mineralocorticoid receptor blockade leads to decreased vascular endothelial function in healthy older adults
Author(s) -
Kim Han Kyul,
Hwang MoonHyon,
Yoo JeungKi,
Luttrell Meredith J.,
Meade Thomas H.,
English Mark W.,
Christou Demetra D.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1165.23
Subject(s) - mineralocorticoid receptor , medicine , eplerenone , enos , endocrinology , aldosterone , blockade , endothelial dysfunction , receptor , nitric oxide , nitric oxide synthase
Mineralocorticoid receptors (MR) modulate vascular endothelial function (VEF) in chronic heart failure and in healthy young adults, but their influence in healthy older adults is unknown. To test the hypothesis that MR modulate VEF in healthy aging, we administered acute MR blockade (MRB: 100 mg Eplerenone for 2 days) in a randomized, double‐blind, placebo‐controlled cross‐over study in 22 adults (8 men, 61±1 y; mean±SE, 53–79 y) free from clinical disease. We measured VEF (brachial flow‐mediated dilation [FMD]; ultrasonography), plasma oxidized LDL and vascular endothelial cell protein expression (VECPE) of eNOS, phosphorylated Ser1177 eNOS (PeNOS), NADPH oxidase (p47‐ phox), nitrotyrosine (NT), and TNF‐α (biopsy coupled with quantitative immunofluorescence) after MRB and placebo. In the overall group, FMD decreased (6.9±0.5 vs. 5.6±0.6%, P=0.02; Eplerenone vs. placebo) with MRB. However, MRB had no effect on oxidized LDL and VECPE of eNOS, PeNOS, p47‐phox, NT and TNF‐α (P≥0.4). Greater decreases in FMD were associated with lower baseline white blood cell and neutrophil (r=0.49, P=0.02 and r=0.57, P=0.006, respectively) and greater lymphocyte (r=−0.53, P=0.01) levels. In conclusion, MR modulate VEF in healthy older adults in an immune cell‐specific manner. MR activation appears to be physiologically important for maintaining vascular function. Supported by NIH Grant AG032067 & AHA Grant 0865117F.