Acute effect of mineralocorticoid receptor antagonism on vascular function in healthy older adults

被引：11

作者：

Hwang, Moon-Hyon ^{[1
,2
]}

Yoo, Jeung-Ki ^{[1
]}

Luttrell, Meredith ^{[3
]}

Kim, Han-Kyul ^{[1
]}

Meade, Thomas H. ^{[4
,5
]}

English, Mark ^{[6
]}

Talcott, Susanne ^{[7
,8
]}

Jaffe, Iris Z. ^{[9
,10
]}

Christou, Demetra D. ^{[1
]}

机构：

[1] Univ Florida, Dept Appl Physiol & Kinesiol, Gainesville, FL 32611 USA

[2] Incheon Natl Univ, Div Hlth & Exercise Sci, Inchon, South Korea

[3] Univ Oregon, Dept Human Physiol, Eugene, OR 97403 USA

[4] Baylor Scott & White Hlth, Dept Cardiol, College Stn, TX USA

[5] Texas A&M Univ, Hlth Sci Ctr, Bryan, TX USA

[6] Baylor Scott & White Hlth, Dept Family & Community Med, College Stn, TX USA

[7] Texas A&M Univ, Dept Nutr & Food Sci, College Stn, TX USA

[8] Texas A&M Univ, Dept Vet Physiol & Pharmacol, College Stn, TX 77843 USA

[9] Tufts Med Ctr, Dept Med, Mol Cardiol Res Inst, Boston, MA USA

[10] Tufts Med Ctr, Dept Med, Div Cardiol, Boston, MA USA

来源：

EXPERIMENTAL GERONTOLOGY | 2016年 / 73卷

关键词：

Aging; Vascular function; Mineralocorticoid receptor; Eplerenone; FLOW-MEDIATED DILATION; NITRIC-OXIDE SYNTHASE; ENDOTHELIAL FUNCTION; OXIDATIVE STRESS; BRACHIAL-ARTERY; HEART-FAILURE; ANGIOTENSIN-II; NADPH OXIDASE; KAPPA-B; ALDOSTERONE;

D O I：

10.1016/j.exger.2015.11.017

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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-termor chronic. Acutemodulation 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, 24 h 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. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：86 / 94

页数：9

共 49 条

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