Natriuretic peptides relax human intrarenal arteries through natriuretic peptide receptor type-A recapitulated by soluble guanylyl cyclase agonists.


Journal

Acta physiologica (Oxford, England)
ISSN: 1748-1716
Titre abrégé: Acta Physiol (Oxf)
Pays: England
ID NLM: 101262545

Informations de publication

Date de publication:
03 2021
Historique:
received: 08 05 2020
revised: 07 08 2020
accepted: 26 09 2020
pubmed: 4 10 2020
medline: 19 8 2021
entrez: 3 10 2020
Statut: ppublish

Résumé

Natriuretic peptides, BNP and ANP increase renal blood flow in experimental animals. The signalling pathway in human kidney vasculature is unknown. It was hypothesized that BNP and ANP cause endothelium-independent relaxation of human intrarenal arteries by vascular natriuretic peptide receptor-A, but not -B and -C, which is mimicked by agonists of soluble guanylyl cyclase sGC. Human (n = 54, diameter: 665 ± 29 µm 95% CI) and control murine intrarenal arteries (n = 83, diameter 300 ± 6 µm 95% CI) were dissected and used for force recording by four-channel wire myography. Arterial segments were pre-contracted, then subjected to increasing concentrations of BNP, ANP, phosphodiesterase 5-inhibitor sildenafil, sGC-activator BAY 60-2770 and -stimulator BAY 41-2272. Endothelial nitric oxide synthase (eNOS) dependence was examined by use of L-NAME and eNOS knockout respectively. Molecular targets (NPR A-C, sGC, phosphodiesterase-5 and neprilysin) were mapped by PCR, immunohistochemistry and RNAscope. BNP, ANP, sildenafil, sGC-activation and -stimulation caused concentration-dependent relaxation of human and murine intrarenal arteries. BNP responses were independent of eNOS and were not potentiated by low concentration of phosphodiesterase-5-inhibitor, sGC-stimulator or NPR-C blocker. PCR showed NPR-A and C, phosphodiesterase-5, neprilysin and sGC mRNA in renal arteries. NPR-A mRNA and protein was observed in vascular smooth muscle and endothelial cells in arteries, podocytes, Bowmans capsule and vasa recta. NPR-C was observed in tubules, glomeruli and vasculature. Activation of transmembrane NPR-A and soluble guanylyl cyclase relax human preglomerular arteries similarly to phosphodiestase-5 inhibition. The human renal arterial bed relaxes in response to cGMP pathway.

Identifiants

pubmed: 33010104
doi: 10.1111/apha.13565
doi:

Substances chimiques

Natriuretic Peptides 0
Guanylate Cyclase EC 4.6.1.2
Soluble Guanylyl Cyclase EC 4.6.1.2
Cyclic GMP H2D2X058MU

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e13565

Informations de copyright

© 2020 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Références

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Auteurs

Andreas Frees (A)

Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.

Kasper B Assersen (KB)

Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.

Mia Jensen (M)

Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.

Pernille B L Hansen (PBL)

Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Research and Early Development, Cardiovascular, Renal and Metabolism, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

Paul M Vanhoutte (PM)

Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.

Kirsten Madsen (K)

Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
Department of Pathology, Odense University Hospital, Odense, Denmark.

Anna Federlein (A)

Institute of Physiology, University of Regensburg, Regensburg, Germany.

Lars Lund (L)

Department of Urology, Odense University Hospital, Odense, Denmark.
Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

Anja Toft (A)

Department of Urology, Odense University Hospital, Odense, Denmark.

Boye L Jensen (BL)

Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.

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