Effects of Eplerenone and Salt Intake on Left Ventricular Remodeling after Myocardial Infarction in Rats

Urabe, Akihiro; Izumi, Tohru; Abe, Yuichi; Taniguchi, Ikuo; Mochizuki, Seibu

doi:10.1291/hypres.29.627

Cited by 13 publications

(8 citation statements)

References 33 publications

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“…This organ damage includes ventricular remodeling [15, 16], renal impairment [17–19], and vascular endothelial dysfunction [20]. Furthermore, aldosterone, which exerts its activity in adipocytes, is involved in abnormal production/secretion of adipocytokines by adipocytes [21] and contributes to increases in oxidative stress [22] and decreases insulin sensitivity in adipose tissue [23, 24].…”

Section: Discussionmentioning

confidence: 99%

Safety and Antihypertensive Effect of Selara® (Eplerenone): Results from a Postmarketing Surveillance in Japan

Takahashi

Hiramatsu

Hotta

et al. 2016

International Journal of Hypertension

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Prospective postmarketing surveillance of Selara (eplerenone), a selective mineralocorticoid receptor antagonist, was performed to confirm its safety and efficacy for hypertension treatment in Japan. The change in blood pressure after initiation of eplerenone treatment was also examined. Patients with essential hypertension who were eplerenone-naïve were recruited regardless of the use of other antihypertensive drugs. For examination of changes in blood pressure, patients were excluded if eplerenone was contraindicated or used off-label. Patients received 50–100 mg of eplerenone once daily and were observed for 12 weeks. No treatments including antihypertensive drugs were restricted during the surveillance period. Across Japan, 3,166 patients were included for safety analysis. The incidence of adverse drug reactions was 2.4%. The major adverse drug reactions observed were hyperkalemia (0.6%), dizziness, renal impairment, and increased serum potassium (0.2% each). The mean systolic blood pressure decreased from 152.1 ± 19.0 mmHg to 134.8 ± 15.2 mmHg at week 12, and the mean diastolic blood pressure decreased from 85.8 ± 13.7 mmHg to 77.7 ± 11.4 mmHg. There were no significant new findings regarding the type or incidence of adverse reactions, and eplerenone had a clinically significant antihypertensive effect, leading to favorable blood pressure control.

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Section: Discussionmentioning

confidence: 99%

Safety and Antihypertensive Effect of Selara® (Eplerenone): Results from a Postmarketing Surveillance in Japan

Takahashi

Hiramatsu

Hotta

et al. 2016

International Journal of Hypertension

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“…Most studies using MR antagonists in a variety of different systems have shown decreases in hypertrophy (40)(41)(42)(43)(44)(45), although not all of them have (26). This effect goes beyond fibrosis in that it shows effects in suppressing the cardiomyocyte expression of the fetal gene program.…”

Section: Figurementioning

confidence: 99%

Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in mice

Usher¹,

Duan²,

Ivaschenko³

et al. 2010

J. Clin. Invest.

321

360

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Inappropriate excess of the steroid hormone aldosterone, which is a mineralocorticoid receptor (MR) agonist, is associated with increased inflammation and risk of cardiovascular disease. MR antagonists are cardioprotective and antiinflammatory in vivo, and evidence suggests that they mediate these effects in part by aldosterone-independent mechanisms. Here we have shown that MR on myeloid cells is necessary for efficient classical macrophage activation by proinflammatory cytokines. Macrophages from mice lacking MR in myeloid cells (referred to herein as MyMRKO mice) exhibited a transcription profile of alternative activation. In vitro, MR deficiency synergized with inducers of alternatively activated macrophages (for example, IL-4 and agonists of PPARγ and the glucocorticoid receptor) to enhance alternative activation. In vivo, MR deficiency in macrophages mimicked the effects of MR antagonists and protected against cardiac hypertrophy, fibrosis, and vascular damage caused by L-NAME/Ang II. Increased blood pressure and heart rates and decreased circadian variation were observed during treatment of MyMRKO mice with L-NAME/Ang II. We conclude that myeloid MR is an important control point in macrophage polarization and that the function of MR on myeloid cells likely represents a conserved ancestral MR function that is integrated in a transcriptional network with PPARγ and glucocorticoid receptor. Furthermore, myeloid MR is critical for blood pressure control and for hypertrophic and fibrotic responses in the mouse heart and aorta.

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“…The cardioprotective effects of eplerenone are blood pressure-independent in mice that lack the gene encoding guanylyl cyclase-A. 9 Urabe et al 10 also showed that eplerenone improved the left ventricular remodeling after myocardial infarction in rats that were fed a high-salt diet but not in those fed a low-salt diet.…”

Section: Salt Aldosterone and Hypertensionmentioning

confidence: 99%

Effects of eplerenone, a selective mineralocorticoid receptor antagonist, on clinical and experimental salt-sensitive hypertension

Takeda

2009

Hypertens Res

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Mineralocorticoid receptors (MRs) are expressed in non-epithelial tissues, such as blood vessels, the heart and adipose tissue. The combined effects of aldosterone and insulin link the metabolic syndrome with hypertension and salt sensitivity. Eplerenone is the newly developed inhibitor of MRs that has significantly fewer adverse effects than similar doses of spironolactone. Eplerenone has been reported to have anti-hypertensive and protective effects on cardiovascular and renal injury in salt-sensitive hypertensive animal models, such as the Dahl salt-sensitive (DS) hypertensive rat and leptin receptor-deficient spontaneously hypertensive rat (SHR/cp). Eplerenone also increases nitric oxide bioavailability and improves impaired endothelial function by decreasing oxidative stress. Clinical studies support the concept that eplerenone is effective for the treatment of salt-sensitive hypertension as well as idiopathic hyperaldosteronism and does not have adverse anti-androgenic adverse effects. In Japan, eplerenone has been used clinically since 2007 for the treatment of hypertension, with its price being marginally lower than all types of angiotensin II receptor antagonists. This will inevitably result in an increasing number of hypertensive patients and those with primary aldosteronism being treated with this agent in the near future. Experimental studies have shown that the profibrotic actions of aldosterone develop only in association with a high-sodium diet. Excess sodium intake is a major contributing factor in the pathogenesis of hypertension, and large population-based studies have shown that there is a significant correlation between the level of salt intake and blood pressure and the frequency of hypertension. In this report, we review the clinical and experimental evidence for the use of the selective receptor antagonist, eplerenone, in the treatment of saltsensitive hypertension. This review also examines how this evidence has contributed to our understanding of the pathophysiological mechanisms of salt-sensitive hypertension.

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Effects of Eplerenone and Salt Intake on Left Ventricular Remodeling after Myocardial Infarction in Rats

Cited by 13 publications

References 33 publications

Safety and Antihypertensive Effect of Selara® (Eplerenone): Results from a Postmarketing Surveillance in Japan

Safety and Antihypertensive Effect of Selara® (Eplerenone): Results from a Postmarketing Surveillance in Japan

Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in mice

Effects of eplerenone, a selective mineralocorticoid receptor antagonist, on clinical and experimental salt-sensitive hypertension

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