Selective Mineralocorticoid Receptor Blocker Eplerenone Reduces Resistance Artery Stiffness in Hypertensive Patients

Abstract

Abstract-Some antihypertensive agents may improve resistance artery remodeling in hypertensive patients whereas other agents may not, for similar blood pressure reduction. We questioned whether the selective mineralocorticoid receptor blocker eplerenone improves resistance artery remodeling in hypertensive patients versus the ␤-blocker atenolol. Sixteen hypertensive patients were randomly assigned to double-blind daily treatment with eplerenone or atenolol. Resistance arteries from gluteal subcutaneous tissue were assessed on a pressurized myograph. After 1 year of treatment, systolic and diastolic blood pressures were similarly well controlled in both groups. Endothelial function did not change with treatment in either group. Media/lumen ratio and cross-sectional area were unchanged in either the atenolol or the eplerenone group. In atenolol-treated patients, the arterial wall became stiffer, whereas in the eplerenone-treated patients, it became less stiff and similar to that of a normotensive control group. The media collagen/elastin ratio was reduced only after eplerenone treatment. Circulating concentrations of osteopontin, monocyte chemoattractant protein-1, basic fibroblast growth factor, interleukin-8, and interleukin-10 were significantly reduced only by eplerenone. However, plasma interleukin-1 receptor a concentration was significantly reduced by both drugs. In conclusion, in hypertensive patients, blood pressure control for 1 year with atenolol was associated with increased wall stiffness of resistance arteries, whereas eplerenone treatment was associated with reduced stiffness, decreased collagen/elastin ratio, and a reduction in circulating inflammatory mediators. These data raise the possibility that eplerenone treatment of hypertensive patients when normalizing blood pressure could potentially be associated with better vascular protection and outcomes than the ␤-blocker atenolol, which remains to be demonstrated. Key Words: aldosterone Ⅲ vascular remodeling Ⅲ extracellular matrix Ⅲ collagen Ⅲ elastin Ⅲ inflammatory biomarkers N ormalization of elevated blood pressure (BP) in hypertensive individuals is associated with reduced targetorgan damage and incident cardiovascular morbidity and mortality. 1 Small artery structural alterations may precede many clinical manifestations of end-organ damage in hypertensive patients 2 and predict the occurrence of future cardiovascular events. 3 Activation of the renin-angiotensinaldosterone system has been associated with increased cardiovascular morbidity and mortality in hypertensive patients. We and others have shown that antihypertensive drugs that interfere with the renin-angiotensin-aldosterone system exert potentially beneficial effects on vascular structure beyond BP control in hypertensive patients at variable risk for cardiovascular disease 4 -7 by improving the functional and anatomic alterations of resistance arteries typically found in experimental and human hypertension and which participate in increased peripheral resistance.Aldosterone is a mine...

Macro and microvasculature in hypertension: therapeutic aspects

“…Recently, a significant reduction in small resistance artery stiffness was observed in essential hypertensive patients treated with a selective mineralocorticoid receptors blocker eplerenone, but not in those treated with atenolol. 20 This beneficial effect was associated with a normalisation of the media collagen/elastin ratio, thus suggesting that antihypertensive treatment may normalize mechanical alterations also in human small resistance arteries.…”

Drug Treatment of Hypertension: Focus on Vascular Health

“…Aldosterone is a mineralocorticoid synthesised by the adrenal cortex and perhaps also in blood vessels 144,145 . It exerts blood pressure elevating effects through interactions with the kidney that influence salt and water balance and may have additional direct effects on blood vessels 56,145,146 .…”

Mineralocorticoid Receptor, the Main Player in Aldosterone-Induced Large Artery Stiffness

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