Atrial natriuretic peptide increases inflammation, infarct size, and mortality after experimental coronary occlusion

Houng, Aiilyan K.; McNamee, Rachel; Kerner, Attila; Sharma, Pritee; Mohamad, Almois; Tronolone, Jonathan; Reed, Guy L.

doi:10.1152/ajpheart.00684.2008

Cited by 17 publications

(14 citation statements)

References 44 publications

(54 reference statements)

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“…Previous studies using similar doses and long continuous infusion of ANP and BNP showed increase of HR (up to 20%) and decrease of MAP (up to 6%), as well as being diuretic [37][38][39][40]. In the pilot study using very high pharmacological doses, we also saw an effect on STA but not on radial artery.…”

Section: Discussionsupporting

confidence: 64%

Effect of natriuretic peptides on cerebral artery blood flow in healthy volunteers

et al. 2015

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Section: Discussionsupporting

confidence: 64%

Effect of natriuretic peptides on cerebral artery blood flow in healthy volunteers

et al. 2015

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“…Our observations of acute proinflammatory roles of ANP and BNP after AMI are in line with previous studies of permanent coronary occlusion or ischemia-reperfusion injury in mice with global, systemic inactivation (knockout) of ANP or GC-A or with transgenic overexpression of BNP in the liver. [32][33][34] However, these former studies have the limitation that systemic arterial hypertension, increased systemic sympathetic and renin-angiotensin activities, and vascular abnormalities influence the cardiac responses of the global knockout mice to ischemia. In the BNP tg mice, 34 the effects of high systemic, pharmacological BNP concentrations were assessed, which may or may not resemble the local high endogenous BNP levels occurring during AMI.…”

Section: Discussion Principal Findingsmentioning

confidence: 99%

Endothelial Actions of ANP Enhance Myocardial Inflammatory Infiltration in the Early Phase After Acute Infarction

Chen

Spitzl

Mathes

et al. 2016

Circulation Research

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Rationale: In patients after acute myocardial infarction (AMI), the initial extent of necrosis and inflammation determine clinical outcome. One early event in AMI is the increased cardiac expression of atrial natriuretic peptide (NP) and B-type NP, with their plasma levels correlating with severity of ischemia. It was shown that NPs, via their cGMP-forming guanylyl cyclase-A (GC-A) receptor and cGMP-dependent kinase I (cGKI), strengthen systemic endothelial barrier properties in acute inflammation. Objective: We studied whether endothelial actions of local NPs modulate myocardial injury and early inflammation after AMI. Methods and Results: Necrosis and inflammation after experimental AMI were compared between control mice and littermates with endothelial-restricted inactivation of GC-A (knockout mice with endothelial GC-A deletion) or cGKI (knockout mice with endothelial cGKI deletion). Unexpectedly, myocardial infarct size and neutrophil infiltration/activity 2 days after AMI were attenuated in knockout mice with endothelial GC-A deletion and unaltered in knockout mice with endothelial cGKI deletion. Molecular studies revealed that hypoxia and tumor necrosis factor-α, conditions accompanying AMI, reduce the endothelial expression of cGKI and enhance cGMP-stimulated phosphodiesterase 2A (PDE2A) levels. Real-time cAMP measurements in endothelial microdomains using a novel fluorescence resonance energy transfer biosensor revealed that PDE2 mediates NP/cGMP-driven decreases of submembrane cAMP levels. Finally, intravital microscopy studies of the mouse cremaster microcirculation showed that tumor necrosis factor-α–induced endothelial NP/GC-A/cGMP/PDE2 signaling impairs endothelial barrier functions. Conclusions: Hypoxia and cytokines, such as tumor necrosis factor-α, modify the endothelial postreceptor signaling pathways of NPs, with downregulation of cGKI, induction of PDE2A, and altered cGMP/cAMP cross talk. Increased expression of PDE2 can mediate hyperpermeability effects of paracrine endothelial NP/GC-A/cGMP signaling and facilitate neutrophil extravasation during the early phase after MI.

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“…What prompted our investigation were the previous experimental evidence that ANP administration increases infarct size and mortality in mice with coronary ligation, 6 and the recent clinical report that the administration of nesiritide, a recombinant form of BNP, failed to affect rehospitalization and risk of death in patients with acute decompensated heart failure. 9 These findings conflicted with the generally held view that natriuretic peptides afford beneficial cardiac and hemodynamic effects.…”

Section: Discussionmentioning

confidence: 99%

“…1;2 Natriuretic peptides are generally viewed as cardioprotective since they were found to reduce blood pressure, plasma volume 3;4 and myocardial infarct size. 5 Yet, other investigators reported an enlargement of infarct size following Atrial Natriuretic Peptide (ANP) administration, 6 and a reduction in infarct size when the natriuretic peptide type A receptor was abrogated or blocked, 7 or when ANP was deleted. 6 Moreover, although natriuretic peptides are thought to retard the progression of heart failure, 8 the administration of recombinant BNP (nesiritide) was recently found to lack protective efficacy in acute heart failure patients.…”

Section: Introductionmentioning

confidence: 99%

“…5 Yet, other investigators reported an enlargement of infarct size following Atrial Natriuretic Peptide (ANP) administration, 6 and a reduction in infarct size when the natriuretic peptide type A receptor was abrogated or blocked, 7 or when ANP was deleted. 6 Moreover, although natriuretic peptides are thought to retard the progression of heart failure, 8 the administration of recombinant BNP (nesiritide) was recently found to lack protective efficacy in acute heart failure patients. 9 Thus, even though natriuretic peptides have been viewed as a compensatory neurohormonal system that is upregulated in the setting of heart failure, affording beneficial cardiac and hemodynamic effects, 8 their role in alleviating cardiac ailments remains unsettled.…”

Section: Introductionmentioning

confidence: 99%

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An Unsuspected Property of Natriuretic Peptides

et al. 2012

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Background Although natriuretic peptides are considered cardioprotective, clinical heart failure trials with recombinant BNP (nesiritide) failed to prove it. Unsuspected proadrenergic effects might oppose the anticipated benefits of natriuretic peptides. Methods and Results We investigated whether natriuretic peptides induce catecholamine release in isolated hearts, sympathetic nerve endings (cardiac synaptosomes) and PC12 cells bearing a sympathetic neuron phenotype. Perfusion of isolated guinea pig hearts with BNP elicited a 3-fold increase in norepinephrine release which doubled in ischemia/reperfusion conditions. BNP and ANP also released norepinephrine from cardiac synaptosomes and dopamine from nerve-growth-factor-differentiated PC12 cells in a concentration-dependent manner. These catecholamine-releasing effects were associated with an increase in intracellular calcium, and abolished by blockade of calcium channels and calcium transients, demonstrating a calcium-dependent exocytotic process. Activation of the guanylyl cyclase-cGMP-protein-kinase-G system with nitroprusside or membrane-permeant cGMP analogs mimicked the proexocytotic effect of natriuretic peptides, an action associated with an increase in intracellular cAMP and protein-kinase-A activity. cAMP enhancement resulted from an inhibition of phosphodiesterase-type-3-induced cAMP hydrolysis. Collectively, these findings indicate that, by inhibiting phosphodiesterase-type-3, natriuretic peptides sequentially enhance intracellular cAMP levels, protein-kinase-A activity, intracellular calcium and catecholamine exocytosis. Conclusions Our results show that natriuretic peptides, at concentrations likely to be reached at cardiac sympathetic nerve endings in advanced congestive heart failure, promote norepinephrine release via a protein-kinase-G-induced inhibition of phosphodiesterase-type-3-mediated cAMP hydrolysis. We propose that this proadrenergic action may counteract the beneficial cardiac and hemodynamic effects of natriuretic peptides, and thus explain the ineffectiveness of nesiritide as a cardiac failure medication.

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Atrial natriuretic peptide increases inflammation, infarct size, and mortality after experimental coronary occlusion

Abstract: Houng AK, McNamee RA, Kerner A, Sharma P, Mohamad A, Tronolone J, Reed GL. Atrial natriuretic peptide increases inflammation, infarct size, and mortality after experimental coronary occlusion.

Cited by 17 publications

References 44 publications

Effect of natriuretic peptides on cerebral artery blood flow in healthy volunteers

Effect of natriuretic peptides on cerebral artery blood flow in healthy volunteers

Endothelial Actions of ANP Enhance Myocardial Inflammatory Infiltration in the Early Phase After Acute Infarction

An Unsuspected Property of Natriuretic Peptides

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