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Natriuretic peptides relax human intrarenal arteries through natriuretic peptide receptor type‐A recapitulated by soluble guanylyl cyclase agonists
Author(s) -
Frees Andreas,
Assersen Kasper B.,
Jensen Mia,
Hansen Pernille B.L.,
Vanhoutte Paul M.,
Madsen Kirsten,
Federlein Anna,
Lund Lars,
Toft Anja,
Jensen Boye L.
Publication year - 2021
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.13565
Subject(s) - medicine , endocrinology , soluble guanylyl cyclase , natriuretic peptide , atrial natriuretic peptide , phosphodiesterase , enos , chemistry , phosphodiesterase 3 , zaprinast , vascular smooth muscle , sildenafil , brain natriuretic peptide , receptor , vasodilation , nitric oxide , nitric oxide synthase , guanylate cyclase , heart failure , biochemistry , smooth muscle , enzyme
Aim 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. Methods 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. Results 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. Conclusion 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.