Plasma Aldosterone Is Increased in Class 2 and 3 Obese Essential Hypertensive Patients Despite Drug Treatment

Sarzani, Riccardo; Guerra, Federico; Mancinelli, Lucia; Buglioni, Alessia; Franchi, Eliana; Dessı̀-Fulgheri, Paolo

doi:10.1038/ajh.2012.47

Cited by 36 publications

(23 citation statements)

References 39 publications

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“…Moreover, in a more recent study, only the most obese patients (BMI 435 kg m À 2 ) were found to have a higher PAC compared with non-obese patients. 29 It is plausible, then, that a nonlinear relationship between body weight and PAC has contributed to inconsistent findings in prior studies. For example, in the Framingham Cohort Study, the mean BMI was 26.6 kg m À 2 , suggesting that the participants were too lean for the association to be detected.…”

Section: Plasma and Urine Aldosterone In Human Obesitymentioning

confidence: 99%

A critical review of the evidence supporting aldosterone in the etiology and its blockade in the treatment of obesity-associated hypertension

Byrd

Brook

2013

J Hum Hypertens

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Obesity is epidemic and is associated with increased blood pressure, which often manifests as treatment-resistant hypertension. Mineralocorticoids have been hypothesized to have a pathogenic role in human obesity-associated hypertension. In this review, we critically appraise the existing data regarding aldosterone in the pathophysiology and treatment of obesity-associated hypertension. We begin by reviewing the mechanisms by which obesity may increase mineralocorticoid activity. We then discuss human studies of plasma and urine aldosterone in obesity and with weight loss. From these studies, we conclude that aldosterone is often, but not always, mildly increased in obesity. Further study is needed to define circumstances in which aldosterone is increased in obesity. We discuss clinical studies in which measures of body size or weight were evaluated as potential predictors of response to mineralocorticoid receptor antagonists. In addition, we review three randomized, controlled clinical trials that exemplify a rigorous approach to determining the role of mineralocorticoid activity in a human disease. We propose that a similar clinical trial is warranted in order to definitively clarify the role of inappropriate mineralocorticoid activity in the etiology of human obesity-associated hypertension. Finally, we conclude that additional research is needed into the possible role of non-aldosterone mineralocorticoids in human obesity-associated hypertension.

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Section: Plasma and Urine Aldosterone In Human Obesitymentioning

confidence: 99%

A critical review of the evidence supporting aldosterone in the etiology and its blockade in the treatment of obesity-associated hypertension

Byrd

Brook

2013

J Hum Hypertens

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“…All RAAS components are increased in visceral adiposity [33, 34]. The abnormal RAAS regulation in obesity appears to be the result of an increased RAAS activity and a defective NPs activity.…”

Section: Cardiovascular and Metabolic Effects Of Cardiac Natriuretic mentioning

confidence: 99%

Cardiac Natriuretic Peptides, Hypertension and Cardiovascular Risk

Sarzani

Spannella

Giulietti

et al. 2017

High Blood Press Cardiovasc Prev

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Prevalence of cardiovascular (CV) disease is increasing worldwide. One of the most important risk factors for CV disease is hypertension that is very often related to obesity and metabolic syndrome. The search for key mechanisms, linking high blood pressure (BP), glucose and lipid dysmetabolism together with higher CV risk and mortality, is attracting increasing attention. Cardiac natriuretic peptides (NPs), including ANP and BNP, may play a crucial role in maintaining CV homeostasis and cardiac health, given their impact not only on BP regulation, but also on glucose and lipid metabolism. The summa of all metabolic activities of cardiac NPs, together with their CV and sodium balance effects, may be very important in decreasing the overall CV risk. Therefore, in the next future, cardiac NPs system, with its two receptors and a neutralizing enzyme, might represent one of the main targets to treat these multiple related conditions and to reduce hypertension and metabolic-related CV risk.

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“…On the other hand, failure of these agents to suppress aldosterone, otherwise referred to as “aldosterone breakthrough” or “aldosterone escape”, is a clinically well-documented phenomenon[46-49] and the efficacy of each agent at inhibiting βarr1-dependent aldosterone production may be inversely proportional to the probability of the ARB to exhibit it. In other words, the more potent βarr1-dependent aldosterone suppressor an ARB is, the lower the likelihood is that the treated patient will suffer from “aldosterone breakthrough”.…”

Section: Implications For Hf Pharmacotherapymentioning

confidence: 99%

Angiotensin receptor blocker drugs and inhibition of adrenal beta-arrestin-1-dependent aldosterone production: Implications for heart failure therapy

Lymperopoulos

Aukszi

2017

WJC

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Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II (AngII). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure (HF), is induced by AngII type 1 receptors (AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1 (βarr1) or -2 (βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 protein-independent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated. Thus, it became apparent that AT1R antagonists that block both pathways equally well are warranted for fully effective aldosterone suppression in HF. This spurred the comparison of all of the currently marketed angiotensin receptor blockers (ARBs, AT1R antagonists or sartans) at blocking activation of the two signaling modes (G protein-, and βarr1-dependent) at the AngII-activated AT1R and hence, at suppression of aldosterone in vitro and in vivo. Although all agents are very potent inhibitors of G protein activation at the AT1R, candesartan and valsartan were uncovered to be the most potent ARBs at blocking βarr activation by AngII and at suppressing aldosterone in vitro and in vivo in post-myocardial infarction HF animals. In contrast, irbesartan and losartan are virtually G protein-“biased” blockers at the human AT1R, with very low efficacy for βarr inhibition and aldosterone suppression. Therefore, candesartan and valsartan (and other, structurally similar compounds) may be the most preferred ARB agents for HF pharmacotherapy, as well as for treatment of other conditions characterized by elevated aldosterone.

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Plasma Aldosterone Is Increased in Class 2 and 3 Obese Essential Hypertensive Patients Despite Drug Treatment

Cited by 36 publications

References 39 publications

A critical review of the evidence supporting aldosterone in the etiology and its blockade in the treatment of obesity-associated hypertension

A critical review of the evidence supporting aldosterone in the etiology and its blockade in the treatment of obesity-associated hypertension

Cardiac Natriuretic Peptides, Hypertension and Cardiovascular Risk

Angiotensin receptor blocker drugs and inhibition of adrenal beta-arrestin-1-dependent aldosterone production: Implications for heart failure therapy

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