Abstract 12385: Effects of Selective Mineralocorticoid Receptor Blocker Eplerenone on Endothelial Function and the Activity of Rho-Associated Kinase in Patients with Essential Hypertension
Background: Hypertension is associated with endothelial dysfunction and activated Rho-associated kinases (ROCKs). Endothelial dysfunction is the initial step of atherosclerosis, leading to cardiovascular complications. ROCKs play an important role in Ca2+ sensitization and vascular resistance. The purpose of this study was to evaluate the effects of selective mineralocorticoid receptor blocker eplerenone on endothelial function and ROCK activity in patients with essential hypertension.
Methods and Results: We evaluated the effects of eplerenone or losaratan treatment for 12 weeks on flow-mediated vasodilation (FMD) using ultrasonography (cuff inflated to 50 mmHg above systolic blood pressure for 5 min) and ROCK activity in peripheral leukocytes by Western blot analysis in 40 untreated hypertensive patients who were randomly divided into an eplerenone group (n=20) and a losaratan group (n=20). ROCK activity was defined as the ratio of phospho myosin-binding subunit (MBS) on myosin light chain phosphatase to total-MBS. There was no significant differences between other parameters, including systemic and forearm hemodynamics, glucose metabolism and lipid profile, in the two groups. Eplerenone increased FMD from 5.6±1.4% to 8.7±1.8% (P<0.05) and decreased leukocyte ROCK activity from 0.79±0.23 to 0.51±0.18 (P<0.05). Losartan increased FMD from 5.4±1.3% to 8.1±1.6% (P<0.05) and did not ROCK activity. Hypotensive effects were similar in the two groups. The expression levels of total-MBS, ROCK1 and ROCK2, and nitroglycerin-induced vasodilation were similar during the follow-up period in the two groups.
Conclusion: Selective mineralocorticoid receptor blocker eplerenone improves endothelial function and inhibits ROCK activity in patients with hypertension.
- © 2011 by American Heart Association, Inc.