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...

Regression of Small Resistance Artery Structural Alterations in Hypertension by Appropriate Antihypertensive Treatment

“…As previously mentioned, vasoconstriction may represent one of the mechanisms leading to eutrophic remodeling as the vasoconstricted state becomes embedded in the newly secreted extracellular matrix. Angiotensin receptor blockers also seem particularly effective in reducing vascular stiffness and collagen content in small resistance arteries [21,22]; stiffness of small arteries (evaluated by stress-strain relationships) was, in fact, enhanced in patients treated with atenolol [23]. In our overview, however, no correlation was observed between changes in brachial pulse pressure and changes in vascular structure when all the available studies were considered together [18••].…”

“…In our overview, however, no correlation was observed between changes in brachial pulse pressure and changes in vascular structure when all the available studies were considered together [18••]. Recently, a significant reduction in small resistance artery stiffness was observed in patients with essential hypertension who were treated with eplerenone, a selective mineralocorticoid receptor blocker, but not in those treated with atenolol [23]. This beneficial effect was associated with normalization of the media collagen: elastin ratio, thus suggesting that antihypertensive treatment also may normalize mechanical alterations in human small resistance arteries.…”

The role of mineralocorticoid receptor antagonists (MRAs) in very old patients with heart failure

“…In a direct comparative study of the beta adrenergic receptor blocking agent, atenolol and the MRA eplerenone in patients with hypertension eplerenone were shown to significantly decrease vascular stiffness independent of a change in blood pressure in comparison with atenolol [14]. In a study of the calcium channel blocking agent, amlodipine and the ARB losartan in patients with hypertension both reduced blood pressure similarly but losartan was more effective in reducing left ventricular mass since the reduction in left ventricular mass was related both to a reduction in blood pressure and plasma aldosterone levels [15].…”

Inflammation and Therapy for Hypertension

“…Lack of pleiotropic effects may explain why atenolol is the least protective of the beta-blockers. This agent does not prevent upregulation of adhesive, inflammatory, prothrombotic, and matrix remodeling proteins in response to oxidants in human endothelial cells; fails to suppress collagen expression, glomerular and interstitial fibrosis, and urine markers of oxidative stress in rats with 5/6 nephrectomy; and does not improve arterial stiffness, overexpression of vascular inflammatory cytokines, growth factors, nitric oxide (NO)-dependent vasodilation, or oxidative stress in hypertensive patients [20].…”