Renin–Angiotensin Blockade Combined With Natriuretic Peptide System Augmentation

Lueder, Thomas G. von; Sangaralingham, S. Jeson; Wang, Bing Hui; Kompa, A.; Atar, Dan; Burnett, John C.; Krum, Henry

doi:10.1161/circheartfailure.112.000289

Cited by 124 publications

(121 citation statements)

References 115 publications

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“…However, our observations in these mice suggest that a local, cardiac imbalance between the activities of the NP/GC-A (inhibition) and aldosterone/MR systems (augmentation), as occurs in patients with HF, can critically contribute to adverse cardiac remodeling. Our observations support current therapeutic concepts that inhibition of the RAA system combined with augmentation of the natriuretic peptide system (with synthetic analogs or by stabilization of the endogenous hormones with inhibitors of the degrading enzyme neutral endopeptidase) 12,13 could help to prevent the transition of compensated cardiac hypertrophy to HF.…”

Section: Perspectivessupporting

confidence: 83%

“…10,11 Consistent with these experimental observations, several approved or investigational treatments of HF enhance intracellular cGMP signaling. 12,13 Of note, cardiac hypertrophy is accompanied by GC-A desensitization which impairs the systemic and also the local actions of ANP and BNP. [14][15][16] As already mentioned, aldosterone levels and MR activity are concomitantly enhanced.…”

mentioning

confidence: 99%

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Atrial Natriuretic Peptide Locally Counteracts the Deleterious Effects of Cardiomyocyte Mineralocorticoid Receptor Activation

Nakagawa

Oberwinkler

Nikolaev

et al. 2014

Circ: Heart Failure

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Background-The endocrine balance between atrial natriuretic peptide (ANP) and the renin-angiotensin-aldosterone system is critical for the maintenance of arterial blood pressure and volume homeostasis. This study investigated whether a cardiac imbalance between ANP and aldosterone, toward increased mineralocorticoid receptor (MR) signaling, contributes to adverse left ventricular remodeling in response to pressure overload.

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Section: Perspectivessupporting

confidence: 83%

mentioning

confidence: 99%

Atrial Natriuretic Peptide Locally Counteracts the Deleterious Effects of Cardiomyocyte Mineralocorticoid Receptor Activation

Nakagawa

Oberwinkler

Nikolaev

et al. 2014

Circ: Heart Failure

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“…11,12 Recently, a new drug class, angiotensin receptor neprilysin inhibitors (ARNi), have been developed to simultaneously block the RAAS and augment NPs through neprilysin inhibition at a presumed lower risk of bradykinin-induced angioedema. 13,14 In a preclinical model, ARNi (using valsartan-candoxatril) provided similar antihypertensive efficacy as omapatrilat without inducing tracheal plasma extravasation (a surrogate of angioedema). 15 LCZ696 has been the first ARNi to be evaluated in patients with hypertension and HF.…”

Section: Clinical Perspective On P 78mentioning

confidence: 99%

Angiotensin Receptor Neprilysin Inhibitor LCZ696 Attenuates Cardiac Remodeling and Dysfunction After Myocardial Infarction by Reducing Cardiac Fibrosis and Hypertrophy

Lueder

Wang

Kompa

et al. 2015

Circ: Heart Failure

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259

190

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“…However, neprilysin inhibitors are ineffective in lowering BP, likely because neprilysin also degrades vasoconstrictor peptides, for example, Ang II and endothelin-1. 75,76 Thus, combining a neprilysin inhibitor with an RAS blocker or an endothelin-converting enzyme inhibitor offers the theoretical advantage of enhancing the favorable vasodilator/natriuretic effects of ANP and BNP and reducing the deleterious vasoconstrictor effects of Ang II or endothelin-1 on BP and target organ damage.…”

Section: Vasopeptidase Inhibitorsmentioning

confidence: 99%

New Approaches in the Treatment of Hypertension

Oparil

Schmieder

2015

Circulation Research

237

137

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Hypertension is the most common modifiable risk factor for cardiovascular disease and death, and lowering blood pressure with antihypertensive drugs reduces target organ damage and prevents cardiovascular disease outcomes. Despite a plethora of available treatment options, a substantial portion of the hypertensive population has uncontrolled blood pressure. The unmet need of controlling blood pressure in this population may be addressed, in part, by developing new drugs and devices/procedures to treat hypertension and its comorbidities. In this Compendium Review, we discuss new drugs and interventional treatments that are undergoing preclinical or clinical testing for hypertension treatment. New drug classes, eg, inhibitors of vasopeptidases, aldosterone synthase and soluble epoxide hydrolase, agonists of natriuretic peptide A and vasoactive intestinal peptide receptor 2, and a novel mineralocorticoid receptor antagonist are in phase II/III of development, while inhibitors of aminopeptidase A, dopamine β-hydroxylase, and the intestinal Na + /H + exchanger 3, agonists of components of the angiotensin-converting enzyme 2/angiotensin(1–7)/Mas receptor axis and vaccines directed toward angiotensin II and its type 1 receptor are in phase I or preclinical development. The two main interventional approaches, transcatheter renal denervation and baroreflex activation therapy, are used in clinical practice for severe treatment resistant hypertension in some countries. Renal denervation is also being evaluated for treatment of various comorbidities, eg, chronic heart failure, cardiac arrhythmias and chronic renal failure. Novel interventional approaches in early development include carotid body ablation and arteriovenous fistula placement. Importantly, none of these novel drug or device treatments has been shown to prevent cardiovascular disease outcomes or death in hypertensive patients.

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Renin–Angiotensin Blockade Combined With Natriuretic Peptide System Augmentation

Cited by 124 publications

References 115 publications

Atrial Natriuretic Peptide Locally Counteracts the Deleterious Effects of Cardiomyocyte Mineralocorticoid Receptor Activation

Atrial Natriuretic Peptide Locally Counteracts the Deleterious Effects of Cardiomyocyte Mineralocorticoid Receptor Activation

Angiotensin Receptor Neprilysin Inhibitor LCZ696 Attenuates Cardiac Remodeling and Dysfunction After Myocardial Infarction by Reducing Cardiac Fibrosis and Hypertrophy

New Approaches in the Treatment of Hypertension

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