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Atrial natriuretic peptide enhances microvascular albumin permeability by the caveolae-mediated transcellular pathway

Please always quote using this URN: urn:nbn:de:bvb:20-opus-126562
  • Aims Cardiac atrial natriuretic peptide (ANP) participates in the maintenance of arterial blood pressure and intravascular volume homeostasis. The hypovolaemic effects of ANP result from coordinated actions in the kidney and systemic microcirculation. Hence, ANP, via its guanylyl cyclase-A (GC-A) receptor and intracellular cyclic GMP as second messenger, stimulates endothelial albumin permeability. Ultimately, this leads to a shift of plasma fluid into interstitial pools. Here we studied the role of caveolae-mediated transendothelial albuminAims Cardiac atrial natriuretic peptide (ANP) participates in the maintenance of arterial blood pressure and intravascular volume homeostasis. The hypovolaemic effects of ANP result from coordinated actions in the kidney and systemic microcirculation. Hence, ANP, via its guanylyl cyclase-A (GC-A) receptor and intracellular cyclic GMP as second messenger, stimulates endothelial albumin permeability. Ultimately, this leads to a shift of plasma fluid into interstitial pools. Here we studied the role of caveolae-mediated transendothelial albumin transport in the hyperpermeability effects of ANP. Methods and results Intravital microscopy studies of the mouse cremaster microcirculation showed that ANP stimulates the extravasation of fluorescent albumin from post-capillary venules and causes arteriolar vasodilatation. The hyperpermeability effect was prevented in mice with conditional, endothelial deletion of GC-A (EC GC-A KO) or with deleted caveolin-1 (cav-1), the caveolae scaffold protein. In contrast, the vasodilating effect was preserved. Concomitantly, the acute hypovolaemic action of ANP was abolished in EC GC-A KO and Cav-1−/− mice. In cultured microvascular rat fat pad and mouse lung endothelial cells, ANP stimulated uptake and transendothelial transport of fluorescent albumin without altering endothelial electrical resistance. The stimulatory effect on albumin uptake was prevented in GC-A- or cav-1-deficient pulmonary endothelia. Finally, preparation of caveolin-enriched lipid rafts from mouse lung and western blotting showed that GC-A and cGMP-dependent protein kinase I partly co-localize with Cav-1 in caveolae microdomains. Conclusion ANP enhances transendothelial caveolae-mediated albumin transport via its GC-A receptor. This ANP-mediated cross-talk between the heart and the microcirculation is critically involved in the regulation of intravascular volume.show moreshow less

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Metadaten
Author: Wen Chen, Birgit Gaßner, Sebastian Börner, Viacheslav O. Nikolaev, Nicolas Schlegel, Jens Waschke, Nadine Steinbronn, Ruth Strasser, Michaela Kuhn
URN:urn:nbn:de:bvb:20-opus-126562
Document Type:Journal article
Faculties:Medizinische Fakultät / Pathologisches Institut
Medizinische Fakultät / Institut für Pharmakologie und Toxikologie
Medizinische Fakultät / Institut für Anatomie und Zellbiologie
Language:English
Parent Title (English):Cardiovascular Research
Year of Completion:2012
Volume:93
Issue:1
Pagenumber:141–151
Source:Cardiovascular Research (2012) 93, 141–151 doi:10.1093/cvr/cvr279
DOI:https://doi.org/10.1093/cvr/cvr279
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:atrial natriuretic peptide; caveolin-1; microvessel permeability
Release Date:2016/07/13
Note:
Lizenzhinweis: The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for noncommercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated.
Licence (German):License LogoDeutsches Urheberrecht