Plasma levels of atrial natriuretic peptide in severe burn injury

Onuoha, Gracey N.; Alpar, E. K.; Gowar, John P

doi:10.1016/s0305-4179(99)00187-4

Cited by 16 publications

(6 citation statements)

References 31 publications

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“…On the other hand, we found that LPS increased ANP mRNA levels in the lungs of wildtype mice. In addition to activation of ANP gene expression, lung injury conditions are associated with decreased number of ANP clearance receptors in the lung endothelium, which promotes retaining of ANP in circulation leading to elevated ANP levels (22,40). LPS-induced activation of ANP is highly consistent with other studies showing a beneficial role of endogenous ANP in other models.…”

Section: Discussionsupporting

confidence: 86%

Atrial natriuretic peptide attenuates LPS-induced lung vascular leak: role of PAK1

Birukova

Xing

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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(ANP) in the models of sepsis, pulmonary edema, and acute respiratory distress syndrome (ARDS) suggest its potential role in the modulation of acute lung injury. We have recently described ANP-protective effects against thrombininduced barrier dysfunction in pulmonary endothelial cells (EC). The current study examined involvement of the Rac effector p21-activated kinase (PAK1) in ANP-protective effects in the model of lung vascular permeability induced by bacterial wall LPS. C57BL/6J mice or ANP knockout mice (Nppa Ϫ/Ϫ ) were treated with LPS (0.63 mg/kg intratracheal) with or without ANP (2 g/kg iv). Lung injury was monitored by measurements of bronchoalveolar lavage protein content, cell count, Evans blue extravasation, and lung histology. Endothelial barrier properties were assessed by morphological analysis and measurements of transendothelial electrical resistance. ANP treatment stimulated Rac-dependent PAK1 phosphorylation, attenuated endothelial permeability caused by LPS, TNF-␣, and IL-6, decreased LPS-induced cell and protein accumulation in bronchoalveolar lavage fluid, and suppressed Evans blue extravasation in the murine model of acute lung injury. More severe LPS-induced lung injury and vascular leak were observed in ANP knockout mice. In rescue experiments, ANP injection significantly reduced lung injury in Nppa Ϫ/Ϫ mice caused by LPS. Molecular inhibition of PAK1 suppressed the protective effects of ANP treatment against LPS-induced lung injury and endothelial barrier dysfunction. This study shows that the protective effects of ANP against LPS-induced vascular leak are mediated at least in part by PAK1-dependent signaling leading to EC barrier enhancement. Our data suggest a direct role for ANP in endothelial barrier regulation via modulation of small GTPase signaling. pulmonary endothelium; permeability; acute lung injury; cytoskeleton; small interfering RNA in vivo ACUTE LUNG INJURY (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), are associated with high morbidity and mortality in patients. During the progression of ALI, the endothelial cell (EC) barrier of the pulmonary vasculature becomes compromised, leading to pulmonary edema, a characteristic feature of ALI. It is well-established that EC barrier dysfunction is initiated by agonist-induced cytoskeletal remodeling, which leads to disruption of cell-cell contacts and formation of paracellular gaps, allowing penetration of protein-rich fluid and inflammatory cells (14, 33). However, far less is known about the processes that determine EC barrier enhancement or protection in the injured lung.Natriuretic peptides (NP) are a family of three peptide hormones: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). Although the major source of ANP is mammalian atrial myocytes, NP are found in other tissues, including aorta, lung, kidney, and brain (2). NP regulate a variety of physiological functions by interacting with receptors at the plasma membrane either to alter le...

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Section: Discussionsupporting

confidence: 86%

Atrial natriuretic peptide attenuates LPS-induced lung vascular leak: role of PAK1

Birukova

Xing

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…On the other hand, decreased number of ANP clearance receptors has been reported in the injured lungs and suggested to retain ANP in circulation (Hollister et al, 1989; Onuoha et al, 2000). These results may illustrate increased NPR-C shedding or degradation under pro-inflammatory conditions without affecting NPR-C mRNA levels.…”

Section: Discussionmentioning

confidence: 99%

Opposite effects of ANP receptors in attenuation of LPS-induced endothelial permeability and lung injury

Xing

Yakubov

Poroyko

et al. 2012

Microvascular Research

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Atrial natriuretic peptide (ANP) has been recently identified as a modulator of acute lung injury (ALI) induced by pro-inflammatory agonists. While previous studies tested effects of exogenous ANP administration, the role of endogenous ANP in the course of ALI remains unexplored. This study examined regulation of ANP and its receptors NPR-A, NPR-B and NPR-C by LPS and involvement of ANP receptors in the modulation of LPS-induced lung injury. Primary cultures of human pulmonary endothelial cells (EC) were used in the in vitro tests. Expression of ANP and its receptors was determined by quantitative RT-PCR analysis. Agonist-induced cytoskeletal remodeling was evaluated by immunofluorescence staining, and EC barrier function was characterized by measurements of transendothelial electrical resistance. In the murine model of ALI, LPS-induced lung injury was assessed by measurements of protein concentration and cell count in bronchoalveolar lavage fluid (BAL). LPS stimulation significantly increased mRNA expression levels of ANP and NPR-A in pulmonary EC. Pharmacological inhibition of NPR-A augmented LPS-induced EC permeability and blocked barrier protective effects of exogenous ANP on LPS-induced intercellular gap formation. In contrast, pharmacological inhibition of ANP clearance receptor NPR-C significantly attenuated LPS-induced barrier disruptive effects. Administration of NPR-A inhibitor in vivo exacerbated LPS-induced lung injury, whereas inhibition of NPR-C suppressed LPS-induced increases in BAL cell count and protein content. These results demonstrate for the first time opposite effects of NPR-A and NPR-C in the modulation of ALI and suggest a compensatory protective mechanism of endogenous ANP in the maintenance of lung vascular permeability in ALI.

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“…19,20 In severely burned patients, elevation of plasma levels of endogenous hANP in the acute phase has been reported. 1,[21][22][23][24] . Plasma concentration of hANP in severely burned patients was first described by Braquet et al 21 and they reported ANP levels were very high on days 1, 5, and 10 postburn.…”

Section: Intravenous Atrial Natriuretic Peptide Postburnmentioning

confidence: 99%

Effect of Intravenous Atrial Natriuretic Peptide on Pulmonary Dysfunction and Renal Function Following Burn Shock

Oda

Kasai

Noborio

et al. 2009

Journal of Trauma: Injury, Infection &Amp; Critical Care

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Plasma levels of atrial natriuretic peptide in severe burn injury

Cited by 16 publications

References 31 publications

Atrial natriuretic peptide attenuates LPS-induced lung vascular leak: role of PAK1

Atrial natriuretic peptide attenuates LPS-induced lung vascular leak: role of PAK1

Opposite effects of ANP receptors in attenuation of LPS-induced endothelial permeability and lung injury

Effect of Intravenous Atrial Natriuretic Peptide on Pulmonary Dysfunction and Renal Function Following Burn Shock

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