Mineralocorticoid receptor blocker eplerenone improves endothelial function and inhibits Rho-associated kinase activity in patients with hypertension

Abstract

Hypertension is associated with endothelial dysfunction and activated Rho-associated kinases (ROCKs). The purpose of this study was to evaluate the effects of the selective mineralocorticoid receptor blocker, eplerenone, on endothelial function and ROCK activity in patients with hypertension. The study was carried out over 48 weeks in 60 untreated patients with hypertension who were randomly assigned to eplerenone, nifedipine, and losartan groups. We evaluated the effects of each treatment on flow-mediated vasodilation (FMD) and ROCK activity in peripheral leukocytes. Eplerenone increased FMD and decreased leukocyte ROCK activity. Nifedipine decreased ROCK activity but did not alter FMD. Losartan increased FMD but did not alter ROCK activity. Hypotensive effects were similar in the three groups, as was nitroglycerin-induced vasodilation during the follow-up period. There were no significant differences between the groups with respect to other parameters. The study results show that eplerenone improves endothelial function and inhibits ROCK activity in patients with essential hypertension.

Figure 1

Flow-mediated vasodilation (FMD) in the eplerenone, nifedipine, and losartan groups before the beginning of treatment (0 weeks) and after 4, 12, and 48 weeks of treatment. *P < 0.05 vs. 0 weeks in the same group.

Figure 2

Representative measurements of the number of circulating progenitor cells (CPCs) by flow cytometry in a patient treated with eplerenone, a patient treated with nifedipine, and a patient treated with losartan before the beginning of treatment (0 weeks) and after 4, 12, and 48 weeks of treatment (top). Comparison of the number of CPCs in patients in the eplerenone, nifedipine, and losartan groups before the beginning of treatment (0 weeks) and after 4, 12, and 48 weeks of treatment (bottom). *P < 0.05 vs. 0 weeks in the same group.

Figure 3

Representative measurements of the migration of circulating progenitor cells (CPCs) labeled with DAPI by fluorescence in a patient treated with eplerenone, a patient treated with nifedipine, and a patient treated with losartan before the beginning of treatment (0 weeks) and after 4, 12, and 48 weeks of treatment (top). Comparison of the migration of CPCs in patients in the eplerenone, nifedipine, and losartan groups before the beginning of treatment (0 weeks) and after 4, 12, and 48 weeks of treatment (bottom). *P < 0.05 vs. 0 weeks in the same group. DAPI, 4’,6-diamidino-2-phenylindole; hpf, high-power field.

Figure 4

Representative data from western blot analysis for phospho-myosin-binding subunit (p-MBS), total-myosin-binding subunit (t-MBS), and β tublin in a patient treated with eplerenone, a patient treated with nifedipine, and a patient treated with losartan before the beginning of treatment (0 weeks) and after 4, 12, and 48 weeks of treatment (top). ROCK activity (p-MBS/t-MBS) in patients in the eplerenone, nifedipine, and losartan groups before the beginning of treatment (0 weeks) and after 4, 12, and 48 weeks of treatment (bottom). *P < 0.05 vs. 0 weeks in the same group.