New agents modulating the renin-angiotensin-aldosterone system—Will there be a new therapeutic option?

Gromotowicz-Popławska, Anna; Szoka, Piotr; Kołodziejczyk, Patrycjusz; Kramkowski, Karol; Wojewódzka-Żelezniakowicz, Marzena; Chabielska, Ewa

doi:10.1177/1535370216660211

Cited by 21 publications

(21 citation statements)

References 130 publications

(152 reference statements)

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“…Gay has questioned the statement about the more intense natriuretic effect of finerenone as compared to the other mineralocorticoid receptor antagonists (MRA). We characterized finerenone as having more natriuretic effects than spironolactone and eplerenone, as stated by other authors [3]. We appreciate Dr.…”

supporting

confidence: 57%

Update in diagnosis and management of primary aldosteronism: reply to a Letter to the Editor

Dick

Queiroz

Brondani

et al. 2018

Clinical Chemistry and Laboratory Medicine (CCLM)

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We have carefully read the comments by Dr. Alain Gay [1] regarding our current review article, in which we describe the investigation and treatment options of primary aldosteronism [2]. Dr. Gay has questioned the statement about the more intense natriuretic effect of finerenone as compared to the other mineralocorticoid receptor antagonists (MRA). We characterized finerenone as having more natriuretic effects than spironolactone and eplerenone, as stated by other authors [3]. We appreciate Dr. Gay's comment and strongly agree that in the studies quoted, natriuresis was not an investigated parameter [4,5]. As a matter of fact, that statement was a speculation based on pharmacodynamics and pharmacokinetics studies that show finerenone to be >500-fold more selective for the mineralocorticoid receptor and to present a 3-10-fold higher potency and efficacy with IC50 (concentration of antagonist required to inhibit 50% activation of receptor) of 18 nmol/L [6,7].In healthy rats, the natriuretic activity of finerenone was tested as a head-to-head comparison of potency and efficacy with the steroidal MRA eplerenone. Both MRAs dose-dependently induced urinary sodium excretion. The application of 1 mg/kg finerenone resulted in similar natriuretic responses as 10 and 30 mg/kg eplerenone, whereas 10 mg/kg finerenone had a comparable natriuretic efficacy as 100 mg/kg eplerenone, suggesting that finerenone represents a more potent MRA [7,8].

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supporting

confidence: 57%

Update in diagnosis and management of primary aldosteronism: reply to a Letter to the Editor

Dick

Queiroz

Brondani

et al. 2018

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…Moreover, liraglutide increased the expression levels of MasR in the lungs of MPFR pups and enhanced the activity of the whole ACE-2/Ang(1–7)/MasR axis in those animals. This axis exerts biological antagonistic actions with respect to the other branches of RAS; the axis conformed by ACE/AII/AT1R [47], and for that, it was also named “vasoprotective axis.” The modulation of the ACE-2/Ang(1–7)/MasR is regarded a novel therapeutic approach to counterbalance the vasoconstrictive, proliferative, and fibrotic actions of ACE/AII/AT1 axis [48]. Moreover, Ang(1–7) reduces lung fibrosis and pulmonary arterial hypertension [49] and activates events that are crucial for the resolution of the inflammatory process of asthma and the promotion of return to lung homeostasis [45].…”

Section: Discussionmentioning

confidence: 99%

Liraglutide Enhances the Activity of the ACE-2/Ang(1–7)/Mas Receptor Pathway in Lungs of Male Pups from Food-Restricted Mothers and Prevents the Reduction of SP-A

Fandino

Vaz

Toba

et al. 2018

International Journal of Endocrinology

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In utero growth restriction and being born small for gestational age are risk factors for respiratory morbidity. IUGR (in utero growth retardation) is associated to overall reduction in lung weight, surfactant content and activity, impaired maturation of the alveolar type II cells, and decreased alveolar formation. The renin-angiotensin system (RAS) may be a key target underlying pathophysiological lung alterations. GLP-1 and agonists of its receptor modulate the expression levels of different components of RAS and also are very important for lung maturation and the production of surfactant proteins. The aim of this study was to elucidate the effects of IUGR induced by perinatal food restriction of the mother in the lung function of pups at early stages of life (PD21) and to determine if liraglutide had any effect during gestational period. Sprague-Dawley pregnant rats were randomly assigned to 50% food restriction (MPFR) or ad libitum control (CT) groups at day of pregnancy 12 (GD12). From GD14 to parturition, pregnant MPFR and CT rats were treated with liraglutide or vehicle. At postnatal day 21 and before weaning, 20 CT and 20 FR male pups were sacrificed and lungs were analyzed by RT-PCR. Liraglutide restored surfactant protein A (SP-A) mRNA expression in pup lungs from food-restricted mothers. Surfactant protein B (SP-B) mRNA expression is not affected by neither IUGR nor liraglutide treatment. Moreover, liraglutide modulated different elements of RAS, increasing angiotensin-converting enzyme 2 (ACE2) and MasR mRNA expression only in pups from food-restricted mothers (MPFR), despite food restriction had not any direct effect at this early stage. Liraglutide also increased endothelial nitric oxide synthase (eNOS) expression in MPFR lungs, reflecting the activation of MasR by angiotensin 1–7. In conclusion, liraglutide prevented the alteration in lung function induced by IUGR and promoted the positive effects of ACE2-Ang(1–7)-MasR in restoring lung function.

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“… 10 , 41 On the other hand, an enhancement of beneficial RAS effects might become possible by selectively blocking classical and enforcing non-classical components in a reinstated, functioning system. 42 …”

Section: Discussionmentioning

confidence: 99%

Molecular remodeling of the renin-angiotensin system after kidney transplantation

Antlanger

Domenig

Kovarík

et al. 2017

J Renin Angiotensin Aldosterone Syst

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Objective:We aimed at assessing the molecular adaptation of the renin-angiotensin system (RAS) after successful kidney transplantation (KTX).Materials and methods:In this prospective, exploratory study we analyzed 12 hemodialysis (HD) patients, who received a KTX and had excellent graft function six to 12 months thereafter. The concentrations of plasma Angiotensin (Ang) peptides (Ang I, Ang II, Ang-(1–7), Ang-(1–5), Ang-(2–8), Ang-(3–8)) were simultaneously quantified with a novel mass spectrometry-based method. Further, renin and aldosterone concentrations were determined by standard immunoassays.Results:Ang values showed a strong inter-individual variability among HD patients. Yet, despite a continued broad dispersion of Ang values after KTX, a substantial improvement of the renin/Ang II correlation was observed in patients without RAS blockade or on angiotensin receptor blocker (HD: renin/Ang II R2 = 0.660, KTX: renin/Ang II R2 = 0.918). Ang-(1–7) representing the alternative RAS axis was only marginally detectable both on HD and after KTX.Conclusions:Following KTX, renin-dependent Ang II formation adapts in non-ACE inhibitor-treated patients. Thus, a largely normal RAS regulation is reconstituted after successful KTX. However, individual Ang concentration variations and a lack of potentially beneficial alternative peptides after KTX call for individualized treatment. The long-term post-transplant RAS regulation remains to be determined.

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New agents modulating the renin-angiotensin-aldosterone system—Will there be a new therapeutic option?

Cited by 21 publications

References 130 publications

Update in diagnosis and management of primary aldosteronism: reply to a Letter to the Editor

Update in diagnosis and management of primary aldosteronism: reply to a Letter to the Editor

Liraglutide Enhances the Activity of the ACE-2/Ang(1–7)/Mas Receptor Pathway in Lungs of Male Pups from Food-Restricted Mothers and Prevents the Reduction of SP-A

Molecular remodeling of the renin-angiotensin system after kidney transplantation

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