The natriuretic peptides BNP and CNP increase heart rate and electrical conduction by stimulating ionic currents in the sinoatrial node and atrial myocardium following activation of guanylyl cyclase-linked natriuretic peptide receptors

Springer, Jeremy E.; Azer, John; Hua, Rui; Robbins, Courtney; Adamczyk, Andrew; McBoyle, Sarah; Bissell, Mary Beth; Rose, Robert A.

doi:10.1016/j.yjmcc.2012.01.018

Cited by 77 publications

(128 citation statements)

References 50 publications

(82 reference statements)

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“…13,28 Human right atrial myocytes were isolated from tissue samples obtained from cardiac surgery patients using similar procedures to those in mice, with some specific modifications as outlined in the Data Supplement. Mouse and human atrial myocytes were used to record APs using the perforated patchclamp technique and I Ca,L and Na + current (I Na ) using the whole-cell patch-clamp technique.…”

Section: Patch Clamping Of Atrial Myocytes From Mice and Humansmentioning

confidence: 99%

“…13,28 Intron spanning primers were designed for human NPR-A, NPR-B, NPR-C, and GAPDH. Experimental protocols and primer sequences are provided in the Data Supplement.…”

Section: Quantitative Polymerase Chain Reactionmentioning

confidence: 99%

“…These measurements demonstrate that neither ANP nor mANP had any effects on mouse atrial AP properties in basal conditions (Figure IB and Tables II and III in the Data Supplement). Because we have previously shown that I Ca,L is a major target of NPs in the atria, 13,15 we also measured the effects of ANP and mANP (100 nmol/L doses) on basal I Ca,L in mouse right atrial myocytes ( Figure IC The absence of effects of ANP on AP morphology and I Ca,L in basal conditions is consistent with our previous studies showing that the related peptides BNP and CNP only affect mouse atrial myocyte electrophysiology in the presence of the β-adrenergic receptor agonist isoproterenol. 13 Accordingly, we next measured the effects of ANP and mANP on AP morphology in mouse atrial myocytes after application of isoproterenol (10 nmol/L).…”

Section: What the Study Addsmentioning

confidence: 99%

“…10 We have recently demonstrated that NPs have potent effects on cardiac electrophysiology. [13][14][15][16] For example, BNP and CNP can increase action potential (AP) duration (APD) in association with increases in L-type Ca 2+ current (I Ca,L ) in atrial myocytes. 13 We have also shown that wild-type NPs (BNP and CNP) can potently increase electrical conduction in the sinoatrial node and atrial myocardium.…”

mentioning

confidence: 99%

“…[13][14][15][16] For example, BNP and CNP can increase action potential (AP) duration (APD) in association with increases in L-type Ca 2+ current (I Ca,L ) in atrial myocytes. 13 We have also shown that wild-type NPs (BNP and CNP) can potently increase electrical conduction in the sinoatrial node and atrial myocardium. 17 Wild-type ANP is able to elicit its physiological effects by binding to 2 NP receptors (NPRs) called NPR-A and NPR-C. 10,18,19 NPR-A is a particulate guanylyl cyclase receptor.…”

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confidence: 99%

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Effects of Wild-Type and Mutant Forms of Atrial Natriuretic Peptide on Atrial Electrophysiology and Arrhythmogenesis

Hua

MacLeod

Polina

et al. 2015

Circ: Arrhythmia and Electrophysiology

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Background-Atrial natriuretic peptide (ANP) is a hormone with numerous beneficial cardiovascular effects. Recently, a mutation in the ANP gene, which results in the generation of a mutant form of ANP (mANP), was identified and shown to cause atrial fibrillation in people. The mechanism(s) through which mANP causes atrial fibrillation is unknown. Our objective was to compare the effects of wild-type ANP and mANP on atrial electrophysiology in mice and humans. Methods and Results-Action potentials (APs), L-type Ca 2+ currents (I Ca,L ), and Na + current were recorded in atrial myocytes from wild-type or natriuretic peptide receptor C knockout (NPR-C −/− ) mice. In mice, ANP and mANP (10-100 nmol/L) had opposing effects on atrial myocyte AP morphology and I Ca,L . ANP increased AP upstroke velocity (V max ), AP duration, and I Ca,L similarly in wild-type and NPR-C −/− myocytes. In contrast, mANP decreased V max , AP duration, and I Ca,L , and these effects were completely absent in NPR-C −/− myocytes. ANP and mANP also had opposing effects on I Ca,L in human atrial myocytes. In contrast, neither ANP nor mANP had any effect on Na + current in mouse atrial myocytes. Optical mapping studies in mice demonstrate that ANP sped electric conduction in the atria, whereas mANP did the opposite and slowed atrial conduction. Atrial pacing in the presence of mANP induced arrhythmias in 62.5% of hearts, whereas treatment with ANP completely prevented the occurrence of arrhythmias. Conclusions-These findings provide mechanistic insight into how mANP causes atrial fibrillation and demonstrate that wildtype ANP is antiarrhythmic.

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Section: Patch Clamping Of Atrial Myocytes From Mice and Humansmentioning

confidence: 99%

“…13,28 Intron spanning primers were designed for human NPR-A, NPR-B, NPR-C, and GAPDH. Experimental protocols and primer sequences are provided in the Data Supplement.…”

Section: Quantitative Polymerase Chain Reactionmentioning

confidence: 99%

Section: What the Study Addsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of Wild-Type and Mutant Forms of Atrial Natriuretic Peptide on Atrial Electrophysiology and Arrhythmogenesis

Hua

MacLeod

Polina

et al. 2015

Circ: Arrhythmia and Electrophysiology

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Physiology of Heart Rate

Quinn

Magder²

2021

Cardiopulmonary Monitoring

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Nesfatin-1 as a novel cardiac peptide: identification, functional characterization, and protection against ischemia/reperfusion injury

Angelone

Filice

Pasqua

et al. 2012

Cell. Mol. Life Sci.

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Nesfatin-1 is an anorexic nucleobindin-2 (NUCB2)-derived hypothalamic peptide. It controls feeding behavior, water intake, and glucose homeostasis. If intracerebrally administered, it induces hypertension, thus suggesting a role in central cardiovascular control. However, it is not known whether it is able to directly control heart performance. We aimed to verify the hypothesis that, as in the case of other hypothalamic satiety peptides, Nesfatin-1 acts as a peripheral cardiac modulator. By western blotting and QT-PCR, we identified the presence of both Nesfatin-1 protein and NUCB2 mRNA in rat cardiac extracts. On isolated and Langendorff-perfused rat heart preparations, we found that exogenous Nesfatin-1 depresses contractility and relaxation without affecting coronary motility. These effects did not involve Nitric oxide, but recruited the particulate guanylate cyclase (pGC) known as natriuretic peptide receptor A (NPR-A), protein kinase G (PKG) and extracellular signal-regulated kinases1/2 (ERK1/2). Co-immunoprecipitation and bioinformatic analyses supported an interaction between Nesfatin-1 and NPR-A. Lastly, we preliminarily observed, through post-conditioning experiments, that Nesfatin-1 protects against ischemia/reperfusion (I/R) injury by reducing infarct size, lactate dehydrogenase release, and postischemic contracture. This protection involves multiple prosurvival kinases such as PKCε, ERK1/2, signal transducer and activator of transcription 3, and mitochondrial K(ATP) channels. It also ameliorates contractility recovery. Our data indicate that: (1) the heart expresses Nesfatin-1, (2) Nesfatin-1 directly affects myocardial performance, possibly involving pGC-linked NPR-A, the pGC/PKG pathway, and ERK1/2, (3) the peptide protects the heart against I/R injury. Results pave the way to include Nesfatin-1 in the neuroendocrine modulators of the cardiac function, also encouraging the clarification of its clinical potential in the presence of nutrition-dependent physio-pathologic cardiovascular diseases.

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The natriuretic peptides BNP and CNP increase heart rate and electrical conduction by stimulating ionic currents in the sinoatrial node and atrial myocardium following activation of guanylyl cyclase-linked natriuretic peptide receptors

Cited by 77 publications

References 50 publications

Effects of Wild-Type and Mutant Forms of Atrial Natriuretic Peptide on Atrial Electrophysiology and Arrhythmogenesis

Effects of Wild-Type and Mutant Forms of Atrial Natriuretic Peptide on Atrial Electrophysiology and Arrhythmogenesis

Physiology of Heart Rate

Nesfatin-1 as a novel cardiac peptide: identification, functional characterization, and protection against ischemia/reperfusion injury

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