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Modulation of the sympathetic nervous system by renal denervation prevents reduction of aortic distensibility in atherosclerosis prone ApoE-deficient rats
- 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.
- Subjects :
- 0301 basic medicine
Sympathetic Nervous System
Apolipoprotein B
Blood Pressure
030204 cardiovascular system & hematology
Kidney
Rats, Sprague-Dawley
Renin-Angiotensin System
Nitroglycerin
Norepinephrine
0302 clinical medicine
Fibrosis
Medicine
Endothelial dysfunction
Aorta
Medicine(all)
Denervation
biology
General Medicine
Vasodilation
Renal sympathetic denervation
Heart Function Tests
Disease Progression
Cardiology
Cardiac function curve
medicine.medical_specialty
ApoE-deficient rats
Hypercholesterolemia
In Vitro Techniques
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Apolipoproteins E
Internal medicine
medicine.artery
Ascending aorta
Animals
Inflammation
Biochemistry, Genetics and Molecular Biology(all)
Aortic distensibility
business.industry
Research
Body Weight
Atherosclerosis
medicine.disease
030104 developmental biology
biology.protein
Arterial stiffness
Carbachol
Endothelium, Vascular
business
Subjects
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