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Modulation of the sympathetic nervous system by renal denervation prevents reduction of aortic distensibility in atherosclerosis prone ApoE-deficient rats

Authors :
Jürgen Geisel
Stephan H. Schirmer
Ulrich Laufs
Björn Hummel
Dominik Linz
Jonas Stroeder
Michael Böhm
Daniel Urban
Mathias Hohl
Andreas Müller
Peter Fries
Thimoteus Speer
Felix Mahfoud
Source :
Journal of Translational Medicine
Publication Year :
2016
Publisher :
Springer Science and Business Media LLC, 2016.

Abstract

Background Apolipoprotein E-deficient (ApoE−/−) rodents spontaneously develop severe hypercholesterolemia and increased aortic stiffness, both accepted risk factors for cardiovascular morbidity and mortality in humans. In patients with resistant hypertension renal denervation (RDN) may improve arterial stiffness, however the underlying mechanisms are incompletely understood. This study investigates the impact of RDN on aortic compliance in a novel atherosclerosis prone ApoE−/−-rat model. Methods Normotensive, 8 weeks old ApoE−/− and Sprague–Dawley (SD) rats were subjected to bilateral surgical RDN (n = 6 per group) or sham operation (n = 5 per group) and fed with normal chow for 8 weeks. Compliance of the ascending aorta was assessed by magnetic resonance imaging. Vasomotor function was measured by aortic ring tension recordings. Aortic collagen content was quantified histologically and plasma aldosterone levels were measured by enzyme-linked immunosorbent assay (ELISA). Results After 8 weeks, ApoE−/−-sham demonstrated a 58 % decrease in aortic distensibility when compared with SD-sham (0.0051 ± 0.0011 vs. 0.0126 ± 0.0023 1/mmHg; p = 0.02). This was accompanied by an impaired endothelium-dependent relaxation of aortic rings and an increase in aortic medial fibrosis (17.87 ± 1.4 vs. 12.27 ± 1.1 %; p = 0.006). In ApoE−/−-rats, RDN prevented the reduction of aortic distensibility (0.0128 ± 0.002 vs. 0.0051 ± 0.0011 1/mmHg; p = 0.01), attenuated endothelial dysfunction, and decreased aortic medial collagen content (12.71 ± 1.3 vs. 17.87 ± 1.4 %; p = 0.01) as well as plasma aldosterone levels (136.33 ± 6.6 vs. 75.52 ± 8.4 pg/ml; p = 0.0003). Cardiac function and metabolic parameters such as hypercholesterolemia were not influenced by RDN. Conclusion ApoE−/−-rats spontaneously develop impaired vascular compliance. RDN improves aortic distensibility and attenuated endothelial dysfunction in ApoE−/−-rats. This was associated with a reduction in aortic fibrosis formation, and plasma aldosterone levels. Electronic supplementary material The online version of this article (doi:10.1186/s12967-016-0914-9) contains supplementary material, which is available to authorized users.

Details

ISSN :
14795876
Volume :
14
Database :
OpenAIRE
Journal :
Journal of Translational Medicine
Accession number :
edsair.doi.dedup.....337e79bf64c0b8009d8f3dbf766b7e18
Full Text :
https://doi.org/10.1186/s12967-016-0914-9