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

被引:9
作者
Kishimoto, Shinji [1 ]
Oki, Kenji [2 ]
Maruhashi, Tatsuya [3 ]
Kajikawa, Masato [4 ]
Matsui, Shogo [3 ]
Hashimoto, Haruki [3 ]
Takaeko, Yuji [3 ]
Kihara, Yasuki [3 ]
Chayama, Kazuaki [5 ]
Goto, Chikara [6 ]
Aibara, Yoshiki [1 ]
Yusoff, Farina Mohamad [1 ]
Nakashima, Ayumu [1 ]
Noma, Kensuke [1 ]
Liao, James K. [7 ]
Higashi, Yukihito [1 ,4 ]
机构
[1] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Cardiovasc Regenerat & Med, Hiroshima, Japan
[2] Hiroshima Univ, Dept Mol & Internal Med, Hiroshima, Japan
[3] Hiroshima Univ, Dept Cardiovasc Med, Grad Sch Biomed & Hlth Sci, Hiroshima, Japan
[4] Hiroshima Univ Hosp, Div Regenerat & Med, Med Ctr Translat & Clin Res, Hiroshima, Japan
[5] Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Dept Gastroenterol & Metab, Hiroshima, Japan
[6] Hiroshima Int Univ, Fac Gen Rehabil, Dpartment Rehabil, Hiroshima, Japan
[7] Univ Chicago, Med Ctr, Sect Cardiol, Chicago, IL 60637 USA
关键词
aldosterone; endothelial function; eplerenone; idiopathic hyperaldosteronism hypertension; mineralocorticoid receptor antagonist; Rho-associated kinases; INTIMA-MEDIA THICKNESS; PRIMARY ALDOSTERONISM; POSSIBLE INVOLVEMENT; VASCULAR FUNCTION; OXIDATIVE STRESS; PROTEIN-KINASE; HYPERTENSION; ATHEROSCLEROSIS; ADRENALECTOMY; VASODILATION;
D O I
10.1097/HJH.0000000000001989
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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.
引用
收藏
页码:1083 / 1095
页数:13
相关论文
共 44 条
  • [11] Endothelial Function and Oxidative Stress in Cardiovascular Diseases
    Higashi, Yukihito
    Noma, Kensuke
    Yoshizumi, Masao
    Kihara, Yasuki
    [J]. CIRCULATION JOURNAL, 2009, 73 (03) : 411 - 418
  • [12] Long-term effect of specific treatment of primary aldosteronism on carotid intima-media thickness
    Holaj, Robert
    Rosa, Jan
    Zelinka, Tomas
    Strauch, Branislav
    Petrak, Ondrej
    Indra, Tomas
    Somloova, Zuzana
    Michalsky, David
    Novak, Kvetoslav
    Wichterle, Dan
    Widimsky, Jiri, Jr.
    [J]. JOURNAL OF HYPERTENSION, 2015, 33 (04) : 874 - 882
  • [13] Intima-Media Thickness of Brachial Artery, Vascular Function, and Cardiovascular Risk Factors
    Iwamoto, Yumiko
    Maruhashi, Tatsuya
    Fujii, Yuichi
    Idei, Naomi
    Fujimura, Noritaka
    Mikami, Shinsuke
    Kajikawa, Masato
    Matsumoto, Takeshi
    Kihara, Yasuki
    Chayama, Kazuaki
    Noma, Kensuke
    Nakashima, Ayumu
    Higashi, Yukihito
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2012, 32 (09) : 2295 - +
  • [14] Rho-Associated Kinase Activity Is a Predictor of Cardiovascular Outcomes
    Kajikawa, Masato
    Noma, Kensuke
    Maruhashi, Tatsuya
    Mikami, Shinsuke
    Iwamoto, Yumiko
    Iwamoto, Akimichi
    Matsumoto, Takeshi
    Hidaka, Takayuki
    Kihara, Yasuki
    Chayama, Kazuaki
    Nakashima, Ayumu
    Goto, Chikara
    Liao, James K.
    Higashi, Yukihito
    [J]. HYPERTENSION, 2014, 63 (04) : 856 - 864
  • [15] Low dose-eplerenone treatment decreases aortic stiffness in patients with resistant hypertension
    Kalizki, Tatjana
    Schmidt, Bernhard M. W.
    Raff, Ulrike
    Reinold, Annemarie
    Schwarz, Thomas K.
    Schneider, Markus P.
    Schmieder, Roland E.
    Schneider, Andreas
    [J]. JOURNAL OF CLINICAL HYPERTENSION, 2017, 19 (07) : 669 - 676
  • [16] Aldosterone administration to mice stimulates macrophage NADPH oxidase and increases atherosclerosis development - A possible role for angiotensin-converting enzyme and the receptors for angiotensin II and aldosterone
    Keidar, S
    Kaplan, M
    Pavlotzky, E
    Coleman, R
    Hayek, T
    Hamoud, S
    Aviram, M
    [J]. CIRCULATION, 2004, 109 (18) : 2213 - 2220
  • [17] Preferential stiffening of central over peripheral arteries in type 2 diabetes
    Kimoto, E
    Shoji, T
    Shinohara, K
    Inaba, M
    Okuno, Y
    Miki, T
    Koyama, R
    Emoto, M
    Nishizawa, Y
    [J]. DIABETES, 2003, 52 (02) : 448 - 452
  • [18] Reactive hyperemia-peripheral arterial tonometry is useful for assessment of not only endothelial function but also stenosis of the digital artery
    Kishimoto, Shinji
    Matsumoto, Takeshi
    Maruhashi, Tatsuya
    Iwamoto, Yumiko
    Kajikawa, Masato
    Oda, Nozomu
    Matsui, Shogo
    Hashimoto, Haruki
    Hidaka, Takayuki
    Kihara, Yasuki
    Chayama, Kazuaki
    Goto, Chikara
    Aibara, Yoshiki
    Yusoff, Farina Binti Mohamad
    Nakashima, Ayumu
    Noma, Kensuke
    Higashi, Yukihito
    [J]. INTERNATIONAL JOURNAL OF CARDIOLOGY, 2018, 260 : 178 - 183
  • [19] Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by rho GTPase
    Laufs, U
    Liao, JK
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (37) : 24266 - 24271
  • [20] Nitroglycerine-Induced Vasodilation for Assessment of Vascular Function A Comparison With Flow-Mediated Vasodilation
    Maruhashi, Tatsuya
    Soga, Junko
    Fujimura, Noritaka
    Idei, Naomi
    Mikami, Shinsuke
    Iwamoto, Yumiko
    Kajikawa, Masato
    Matsumoto, Takeshi
    Hidaka, Takayuki
    Kihara, Yasuki
    Chayama, Kazuaki
    Noma, Kensuke
    Nakashima, Ayumu
    Goto, Chikara
    Higashi, Yukihito
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2013, 33 (06) : 1401 - +