Aldosterone breakthrough during therapy with angiotensin‐converting enzyme inhibitors and angiotensin II receptor blockers in proteinuric patients with immunoglobulin A nephropathy

Horita, Yuki; Taura, Koichi; Taguchi, Takashi; Furusu, Akira; Kohno, Shigeru

doi:10.1111/j.1440-1797.2006.00665.x

Cited by 71 publications

(42 citation statements)

References 25 publications

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“…[20][21][22] ALD breakthrough generally occurs in about half of the cases within 12 months. 23,24 Recently, ALD breakthrough was observed in 23% of hypertensive patients during candesartan treatment. 25 The elevation of Ang II after treatment with ARBs may contribute to ALD breakthrough due to the activation of AT type 2 receptor in the adrenal gland.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the long-term effects of candesartan and olmesartan on plasma angiotensin II and left ventricular mass index in patients with hypertension

et al. 2009

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In general, treatment with most angiotensin receptor blockers (ARBs) increases plasma angiotensin II (Ang II) level because of a lack of negative feedback on renin activity. Olmesartan is a potential ARB inducing activation of angiotensin-converting enzyme 2 (ACE2) that hydrolyzes Ang II to Ang 1-7, and has shown a beneficial effect on ventricular remodeling. Indeed, a previous study reported that olmesartan treatment resulted in decreased plasma levels of Ang II and aldosterone. However, there has not yet been a study showing the relationship of chronic effects of olmesartan on Ang II and the left ventricular mass index (LVMI) in comparison with those of other ARB. A total of 50 stable outpatients with essential hypertension who had received candesartan for more than 1 year were randomized into two groups: control group (n¼25): continuous candesartan treatment at a stable dose; and olmesartan group (n¼25): candesartan (8 mg day À1 ) was changed to olmesartan given at a dose of 20 mg day À1 . There was no difference in the baseline characteristics between the two groups. In the control group, there were no significant changes in blood pressure, LVMI or biomarkers during 12 months of study. In the olmesartan group, blood pressure did not change and plasma levels of Ang II decreased during 12 months of study, whereas LVMI was significantly decreased after 12 months (135 ± 36 vs. 123 ± 29 g m À2 ; Po0.01). These findings indicate that replacing candesartan with olmesartan decreased LVMI in association with a sustained decrease of plasma Ang II over a 12-month period without changing blood pressure or plasma aldosterone in patients with essential hypertension.

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Section: Discussionmentioning

confidence: 99%

Comparison of the long-term effects of candesartan and olmesartan on plasma angiotensin II and left ventricular mass index in patients with hypertension

et al. 2009

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“…1,5-11 ALD breakthrough generally occurs in about half of the cases within 12 months. 8, 17 The incidence of ALD breakthrough depends on the length of the follow-up period. 18 In previous studies that defined breakthrough as any increase from an individual's baseline ALD level, the incidence ranged from 10% over 6 months to 53% over 12 months.…”

Section: Discussionmentioning

confidence: 99%

“…8,[14][15][16]19,20 In this study, the follow-up period was 18 months and the incidence of ALD breakthrough was 7% with efonidipine treatment, which was relatively low compared with that in previous studies. 8,[14][15][16][17]19,20 Moreover, in our study, all patients had already been receiving ACE-I or ARB for more than 1 year, suggesting that some patients had ALD breakthrough. In this population, only two patients (7%) had ALD breakthrough after the replacement of amlodipine with efonidipine, suggesting the usefulness of the combination of ACE-I or ARB and efonidipine.…”

Section: Hypertension Researchmentioning

confidence: 99%

Long-term effect of efonidipine therapy on plasma aldosterone and left ventricular mass index in patients with essential hypertension

et al. 2009

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A certain percentage of aldosterone (ALD) breakthrough generally occurs in patients with hypertension and chronic heart failure and is an important issue during long-term treatment with angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB). It has been reported that efonidipine decreases the plasma levels of ALD. However, the long-term effects of efonidipine on the plasma levels of ALD and the left ventricular mass index (LVMI) remain unknown in patients with hypertension. Sixty stable outpatients with essential hypertension who had received amlodipine and ACE-I or ARB for more than 1 year were randomized into two groups (amlodipine group (n¼30): continuous amlodipine treatment at a stable dose; efonidipine group (n¼30): amlodipine (5 mg day À1 ) was changed to efonidipine at a dose of 40 mg day À1 ). There was no difference in their baseline characteristics including the LVMI and plasma levels of ALD. In the amlodipine group, there were no significant changes in blood pressure, LVMI or plasma levels of ALD for 18 months. In the efonidipine group, blood pressure did not change after replacement of amlodipine with efonidipine, although there was a significant decrease in the plasma levels of ALD after 6 months. The decrease in ALD was sustained for 18 months and LVMI was significantly decreased after 18 months (121 ± 25 vs. 114 ± 21 g m À2 , Po0.05). There was a significant correlation between the changes in LVMI and % changes of ALD in the efonidipine group. These findings indicate that the effect of efonidipine on the suppression of plasma ALD was sustained for at least 18 months and that long-term efonidipine therapy decreases LVMI in patients with essential hypertension. INTRODUCTIONRecent clinical trials have shown that inhibiting the biological actions of aldosterone (ALD) using an ALD blocker alone or in combination with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB) is reported to be a useful add-on therapy in hypertensive patients, reducing the incidence of cardiovascular events among patients with chronic heart failure (CHF). 1,2 Therefore, to prevent cardiovascular disease, targeting ALD synthesis and release may be clinically important. One of the major incentives for implementing the RALES and EPHESUS trial was the investigation of the ALD breakthrough phenomenon 3,4 in which ACE-I does not reliably induce significant decreases in plasma ALD levels. Therefore, in a certain percentage of patients with hypertension or CHF, ALD breakthrough generally occurs. This phenomenon is an important issue during a long-term treatment with ACE-I and ARB. 1,[5][6][7][8][9][10][11] Although the mechanisms of ALD breakthrough remain obscure, there was no apparent reduction of the left ventricular mass index (LVMI) in patients with ALD breakthrough(+) during the administration of ACE-I. 8 Aldosterone production in the adrenal gland is mediated mainly by the T-type calcium channel in vitro. 12 Recently, it has been reported that efonidipine, a...

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“…In addition, the degree to which each ARB prevents arr activation by the AngII-bound adrenocortical AT1R might underlie the "aldosterone breakthrough" phenomenon that often hampers the clinical use of these agents [8][9][10] . Given that all ARBs appear more or less equally potent at blocking the G protein-dependent component of the AT1R signaling towards aldosterone production in the AZG cells, but display significant differences in their potencies at blocking the arr component, it is quite plausible that the adrenal arr-dependent aldosterone production pathway is responsible for the manifestation of the "aldosterone breakthrough" phenomenon upon ARB use, and, the stronger inhibitor of this pathway an ARB drug is, the lower the risk of this side-effect.…”

Section: Research Highlightmentioning

confidence: 99%

“…This phenomenon (i.e. failure at suppressing aldosterone) has been observed with several ARBs clinically and is sometimes referred to as "aldosterone breakthrough" [7][8][9][10] . Together,…”

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confidence: 99%

Which ARB drug is better for heart failure therapy? Aldosterone suppression holds the answer

McCrink¹,

Brill

Lymperopoulos

2015

Receptor Clin Invest

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The known physiological effect of angiotensin II (AngII) type I receptors (AT1Rs), synthesis and secretion of the cardiotoxic hormone aldosterone, whose elevation accompanies and aggravates heart failure (HF), is mediated by both G proteins and arrestins (arrs). We recently examined the relative potencies of all the currently used in the clinic AT1R antagonist drugs (angiotensin receptor blockers, ARBs, or sartans) at preventing activation of either of these two signaling mediators at the AngII-bound AT1R and, consequently, at suppression of aldosterone in vitro and in vivo. We also tested the impact of the aldosterone suppression they produce in vivo on the cardiac function of post-myocardial infarction (MI) animals progressing to HF. By using a variety of techniques in cultured cells in vitro, we found that all ARBs are potent inhibitors of G protein activation at the AT1R but display striking differences in their potency at blocking the second signaling component of aldosterone production in the adrenal cortex, i.e. arrs. Candesartan and valsartan in particular were found the most potent at blocking AngII-induced arr activation at this receptor, translating into excellent efficacies at aldosterone suppression in vitro and in vivo and at post-MI cardiac function and remodeling amelioration. Conversely, irbesartan appears to be largely G protein-inhibitory, as it exhibits very low potency towards arr inhibition. As a result, it is a very weak aldosterone suppressor in vitro and in vivo, and fails to improve cardiac function or adverse remodeling post-MI. These findings will aid pharmacotherapeutic decisions for therapy of post-MI HF and they will also help develop novel and better ARB drugs, with greater efficacy for HF therapy.

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Aldosterone breakthrough during therapy with angiotensin‐converting enzyme inhibitors and angiotensin II receptor blockers in proteinuric patients with immunoglobulin A nephropathy

Cited by 71 publications

References 25 publications

Comparison of the long-term effects of candesartan and olmesartan on plasma angiotensin II and left ventricular mass index in patients with hypertension

Comparison of the long-term effects of candesartan and olmesartan on plasma angiotensin II and left ventricular mass index in patients with hypertension

Long-term effect of efonidipine therapy on plasma aldosterone and left ventricular mass index in patients with essential hypertension

Which ARB drug is better for heart failure therapy? Aldosterone suppression holds the answer

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