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

a pilot study

Kishimoto, Shinjia; Oki, Kenjib; Maruhashi, Tatsuyac; Kajikawa, Masatod; Matsui, Shogoc; Hashimoto, Harukic; Takaeko, Yujic; Kihara, Yasukic; Chayama, Kazuakie; Goto, Chikaraf; Aibara, Yoshikia; Yusoff, Farina Mohamada; Nakashima, Ayumua; Noma, Kensukea; Liao, James K.g; Higashi, Yukihitoa,d

doi: 10.1097/HJH.0000000000001989
ORIGINAL PAPERS: Secondary hypertension
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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 ± 0.04 mm, P = 0.14).

Conclusion: Eplerenone improves microvascular endothelial function, vascular smooth muscle function, arterial stiffness and ROCK activity in patients with IHA.

Clinical Trial Registration Information: URL for Clinical Trial: http://UMIN; Registration Number for Clinical Trial: UMIN000003409

aDepartment of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine

bDepartment of Molecular and Internal Medicine

cDepartment of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University

dDivision of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital

eDepartment of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University

fDpartment of Rehabilitation, Faculty of General Rehabilitation, Hiroshima International University, Hiroshima, Japan

gSection of Cardiology, University of Chicago Medical Center, Illinois, USA

Correspondence to Yukihito Higashi, MD, PhD, FAHA, Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Tel: +81 82 257 5831; fax: +81 82 257 5831; e-mail: yhigashi@hiroshima-u.ac.jp.

Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; APA, aldosterone-producing adenoma; ARB, angiotensin II receptor blocker; ARR, aldosterone-to-renin ratio; baPWV, brachial–ankle pulse wave velocity; BUN, blood urea nitrogen; EHT, essential hypertension; FMD, flow-mediated vasodilation; HDL, high-density lipoprotein; IHA, idiopathic hyperaldosteronism; IMT, intima-media thickness; LDL, low-density lipoprotein; MLCPh, myosin light chain phosphatase; NID, nitroglycerine-induced vasodilation; NO, nitric oxide; PA, primary aldosteronism; PAC, plasma aldosterone concentration; PRA, plasma renin activity; RHI, reactive hyperemia index; RH-PAT, reactive hyperemia -peripheral arterial tonometry; ROCK, Rho-associated kinase

Received 10 August, 2018

Accepted 8 October, 2018

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