Eplerenone improves endothelial function and arterial stiffness and inhibits Rho-associated kinase activity in patients with idiopathic hyperaldosteronism

Abstract

Objective: Primary aldosteronism is one of the most common cause of secondary hypertension. It is well known that the incidence of cardiovascular events is higher in patients with primary aldosteronism than in patients with essential hypertension. In a previous study, we showed that aldosterone-producing adenoma is associated with vascular function and structure. The aim of this study was to evaluate the effects of eplerenone on vascular function in the macrovasculature and microvasculature, arterial stiffness and Rho-associated kinase (ROCK) activity in patients with idiopathic hyperaldosteronism (IHA). Methods: Vascular function, including reactive hyperemia index (RHI), flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID), arterial stiffness including brachial–ankle pulse wave velocity (baPWV) and brachial intima–media thickness (IMT) and ROCK activity in peripheral leukocytes were measured before and after 12 weeks of treatment with eplerenone in 50 patients with IHA. Results: After 12 weeks, eplerenone decreased the aldosterone renin ratio but did not alter SBP and DBP. Eplerenone treatment increased log RHI from 0.56 ± 0.25 to 0.69 ± 0.25 (P< 0.01) and NID from 12.8 ± 5.8 to 14.9 ± 6.9% (P = 0.02) and it decreased baPWV from 1540± 263 to 1505 ±281 (P = 0.04) and ROCK activity from 1.20 ± 0.54 to 0.89 ± 0.42 (P< 0.01), whereas there was no significant change in FMD (increase from 4.6 ± 3.4 to 4.6±3.6%, P = 0.99) or brachial IMT (decrease from 0.28±0.07 to 0.28±0.04mm, P = 0.14). Conclusion: Eplerenone improves microvascular endothelial function, vascular smooth muscle function, arterial stiffness and ROCK activity in patients with IHA.

The epoxyeicosatrienoic pathway is intact in endothelial and smooth muscle cells exposed to aldosterone excess

“…In particular, renal injury, atrial fibrillation, coronary artery disease and stroke even when compared to essentially hypertensive control patients who had been matched for age, sex and blood pressure are more abundant in patients with PA. One of the earliest steps in the pathogenesis of atherosclerosis is endothelial dysfunction[3]. In line with previous observations indicating a high prevalence of atherosclerotic disease, endothelial dysfunction has been demonstrated in patients with PA[4–6]. Endothelial dysfunction is a descriptive term which does not allow for a mechanistic attribution.…”

Primary aldosteronism and coronary-pulmonary artery fistula: coincidence or causal link? A case report and literature review

“…Aldosterone-induced MR-dependent proliferation was confirmed ex vivo in human endothelial cells and the pharmacological-specific blockade of the MR by eplerenone inhibited endothelial proliferation in a rat model of heart failure [7]. Recently, Rho-associated kinase (ROCK) activity has drawn attention for its crucial role in angiogenesis [15] and the treatment with eplerenone for 12 weeks improves arterial stiffness, vascular smooth muscle function and microvascular endothelial function, and inhibits ROCK activity in patients with PA [16].…”

Hydrochlorothiazide Reduces Cardiac Hypertrophy, Fibrosis and Rho-Kinase Activation in DOCA-Salt Induced Hypertension

“…In hypertensive patients, the mineralocorticoid (MR) receptor blocker eplerenone reduces blood pressure, improves endothelial function, and inhibits ROCK activity 62 and in patients with hyperaldosteronism it improves endothelial function, arterial stiffness and inhibits ROCK activity. 63 In obesity-associated nephropathy in C57BL/6 J mice, renal injury is mediated by mineralocorticoid receptor activation in the kidney and subsequent ROCK stimulation. 64 Furthermore, in obese db/db mice with hyperaldosteronism there is vascular MR hyperactivation, dysfunction and remodeling, increased ROCK signaling and higher expression of pro-inflammatory and pro-fibrotic markers.…”