Frees, Andreas and Assersen, Kasper B. and Jensen, Mia and Hansen, Pernille B. L. and Vanhoutte, Paul M. and Madsen, Kirsten and Federlein, Anna and Lund, Lars and Toft, Anja and Jensen, Boye L. (2021) Natriuretic peptides relax human intrarenal arteries through natriuretic peptide receptor type-A recapitulated by soluble guanylyl cyclase agonists. ACTA PHYSIOLOGICA, 231 (3): e13565. ISSN 1748-1708, 1748-1716
Full text not available from this repository. (Request a copy)Abstract
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 mu m 95% CI) and control murine intrarenal arteries (n = 83, diameter 300 +/- 6 mu m 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLOMERULAR-FILTRATION-RATE; HEART-FAILURE; ATRIOPEPTIN-III; PRESSURE; ANP; VASOCONSTRICTION; ENDOTHELIUM; AFFERENT; KIDNEY; cGMP; endothelium; eNOS; hypertension; kidney |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Frank Schweda |
| Depositing User: | Petra Gürster |
| Date Deposited: | 21 Apr 2021 08:30 |
| Last Modified: | 21 Apr 2021 08:30 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43409 |
Actions (login required)
 |
View Item |
