Aldosterone, Hypertension, and Antihypertensive Therapy: Insights From a General Population

Cannone, Valentina; Buglioni, Alessia; Sangaralingham, S. Jeson; Scott, Christopher G.; Bailey, Kent R.; Rodeheffer, Richard J.; Redfield, Margaret M.; Sarzani, Riccardo; Burnett, John C.

doi:10.1016/j.mayocp.2018.05.027

Cited by 10 publications

(14 citation statements)

References 32 publications

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“…Furthermore, recent data show that even in primary aldosteronism femur and spine BMD and TBS are reduced (135,136) and that the fracture risk is increased (137,138). This clinical picture as well as fracture risk recedes after treatment, particularly after surgery (139). Since aldosterone secretion is increased in a large part of hypertensive patients (139), altogether these data may suggest that cortisol and aldosterone secretion may represent two so far ignored contributors to osteoporosis in the general population.…”

Section: Discussionmentioning

confidence: 99%

DIAGNOSIS OF ENDOCRINE DISEASE: Evaluation of bone fragility in endocrine disorders

Eller-Vainicher

Falchetti

Gennari

et al. 2019

European Journal of Endocrinology

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An underlying disease affecting bone health is present in up to 40 and 60% of osteoporotic postmenopausal women and men respectively. Among the disorders leading to a secondary form of osteoporosis, the endocrine diseases are highly represented. A frequent finding in patients affected with an endocrine-related forms of bone disease is that the skeletal fragility is partially independent of the bone density, since the fracture risk in these patients is related more to a reduction of bone quality than to a decrease of bone mass. As a consequence, bone mineral density evaluation by dual-X-ray absorptiometry may be inadequate for establishing the risk of fracture in the setting of the endocrine-related forms of osteoporosis. In the recent years, several attempts to non-invasively estimating bone quality have been done. Nowadays, some new tools are available in the clinical practice for optimising the fracture risk estimation in patients with endocrine disorders. The aim of this review is to summarise the evidence regarding the role of the different imaging tools for evaluating bone density and bone quality in the most frequent forms of endocrine-related osteoporosis, such as obesity, diabetes, acromegaly, thyrotoxicosis, primary hyperparathyroidism, hypercortisolism and hypogonadism. For each of these disorders, data regarding both the current available tools and the future possible new techniques for assessing bone fragility in patients with endocrine diseases are reported.

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Section: Discussionmentioning

confidence: 99%

DIAGNOSIS OF ENDOCRINE DISEASE: Evaluation of bone fragility in endocrine disorders

Eller-Vainicher

Falchetti

Gennari

et al. 2019

European Journal of Endocrinology

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“…Probably the lack of adequate circulating ANP contributes to the onset of hypertension and increases the risk for cardiovascular diseases. In addition, recent epidemiological studies reveal an inverse relationship between aldosterone and ANP circulating levels in the general community and hypertensive subjects, with aldosterone being higher in the presence of lower ANP levels [12,13]. Interestingly, heart failure also appears to be a state of ANP deficiency based on a study conducted by Reginauld and coworkers [14].…”

Section: Introductionmentioning

confidence: 99%

Atrial Natriuretic Peptide: A Molecular Target of Novel Therapeutic Approaches to Cardio-Metabolic Disease

Cannone

Cabassi

Volpi

et al. 2019

IJMS

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Atrial natriuretic peptide (ANP) is a cardiac hormone with pleiotropic cardiovascular and metabolic properties including vasodilation, natriuresis and suppression of the renin-angiotensin-aldosterone system. Moreover, ANP induces lipolysis, lipid oxidation, adipocyte browning and ameliorates insulin sensitivity. Studies on ANP genetic variants revealed that subjects with higher ANP plasma levels have lower cardio-metabolic risk. In vivo and in humans, augmenting the ANP pathway has been shown to exert cardiovascular therapeutic actions while ameliorating the metabolic profile. MANP is a novel designer ANP-based peptide with greater and more sustained biological actions than ANP in animal models. Recent studies also demonstrated that MANP lowers blood pressure and inhibits aldosterone in hypertensive subjects whereas cardiometabolic properties of MANP are currently tested in an on-going clinical study in hypertension and metabolic syndrome. Evidence from in vitro, in vivo and in human studies support the concept that ANP and related pathway represent an optimal target for a comprehensive approach to cardiometabolic disease.

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“…HTN and HF). Patients with HTN, and also patients with HF, have disturbed neurohumoral balance, which is characterized by NP-deficiency and RAS activation [53][54][55] . Treatment with drugs that target both the pGC-A receptor system and MasR may thus have the potential to restore neurohumoral balance in HTN and HF.…”

Section: Discussionmentioning

confidence: 99%

Design, Synthesis, and Actions of an Innovative Bispecific Designer Peptide

et al. 2019

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Despite optimal current therapies, cardiovascular disease (CVD) remains the leading cause for death worldwide. Importantly, advances in peptide engineering have accelerated the development of innovative therapeutics for diverse human disease states. Additionally, the advancement of bispecific therapeutics targeting more than one signaling pathway represents a highly innovative strategy for the treatment of CVD. We therefore engineered a novel designer peptide which simultaneously targets the particulate guanylyl cyclase A (pGC-A) receptor and the Mas-receptor (MasR), potentially representing an attractive cardiorenoprotective therapeutic for CVD. We engineered a novel, bispecific receptor activator, NPA7 that represents the fusion of a 22-amino acid sequence of B-type natriuretic peptide (an endogenous ligand of pGC-A) with Angiotensin 1-7 (ANG1-7), the 7-amino acid endogenous activator of MasR. We assessed NPA7's dual receptor activating actions in vitro (second messenger production and receptor interaction). Further, we performed an intravenous peptide infusion comparison study in normal canines to study its biological actions in vivo, including in the presence of a MasR antagonist. Our in vivo and in vitro studies demonstrate the successful synthesis of NPA7 as a bispecific receptor activator targeting pGC-A and MasR. In normal canines, NPA7 possesses enhanced natriuretic, diuretic, systemic and renal vasorelaxing and cardiac unloading properties. Importantly, NPA7s actions are superior to that of the individual native pGC-A or MasR ligands. These studies advance NPA7 as a novel bispecific designer peptide with potential cardiorenal therapeutic benefit for the treatment of CVD such as hypertension and heart failure.

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Aldosterone, Hypertension, and Antihypertensive Therapy: Insights From a General Population

Cited by 10 publications

References 32 publications

DIAGNOSIS OF ENDOCRINE DISEASE: Evaluation of bone fragility in endocrine disorders

DIAGNOSIS OF ENDOCRINE DISEASE: Evaluation of bone fragility in endocrine disorders

Atrial Natriuretic Peptide: A Molecular Target of Novel Therapeutic Approaches to Cardio-Metabolic Disease

Design, Synthesis, and Actions of an Innovative Bispecific Designer Peptide

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