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



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).



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.



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.
Klinik für Innere Medizin III, Universität des Saarlandes, 66421, Homburg/Saar, Germany. Mathias.Hohl@uks.eu.
Mathias
M
Hohl
Klinik für Innere Medizin III, Universität des Saarlandes, 66421, Homburg/Saar, Germany.
Dominik
D
Linz
Klinik für Diagnostische und Interventionelle Radiologie, Universität des Saarlandes, Homburg/Saar, Germany.
Peter
P
Fries
Klinik für Diagnostische und Interventionelle Radiologie, Universität des Saarlandes, Homburg/Saar, Germany.
Andreas
A
Müller
Klinik für Diagnostische und Interventionelle Radiologie, Universität des Saarlandes, Homburg/Saar, Germany.
Jonas
J
Stroeder
Klinik für Innere Medizin III, Universität des Saarlandes, 66421, Homburg/Saar, Germany.
Daniel
D
Urban
Klinik für Innere Medizin IV, Universität des Saarlandes, Homburg/Saar, Germany.
Thimoteus
T
Speer
Zentrallabor, Klinische Chemie und Laboratorium Medizin, Universität des Saarlandes, Homburg/Saar, Germany.
Jürgen
J
Geisel
Institut für Klinische Hämostaseologie und Transfusionsmedizin, Universität des Saarlandes, Homburg/Saar, Germany.
Björn
B
Hummel
Klinik für Innere Medizin III, Universität des Saarlandes, 66421, Homburg/Saar, Germany.
Ulrich
U
Laufs
Klinik für Innere Medizin III, Universität des Saarlandes, 66421, Homburg/Saar, Germany.
Stephan H
SH
Schirmer
Klinik für Innere Medizin III, Universität des Saarlandes, 66421, Homburg/Saar, Germany.
Michael
M
Böhm
Klinik für Innere Medizin III, Universität des Saarlandes, 66421, Homburg/Saar, Germany.
Felix
F
Mahfoud
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D001057:Apolipoproteins E / Q000172:deficiency* / Q000378:metabolism; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D003714:Denervation; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000503:physiopathology; D005355:Fibrosis; D006334:Heart Function Tests; D066298:In Vitro Techniques; D007249:Inflammation / Q000473:pathology; D007668:Kidney / Q000294:innervation* / Q000503:physiopathology; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects
D001057:Apolipoproteins E; D002217:Carbachol; D005996:Nitroglycerin; D009638:Norepinephrine
Aortic distensibility; ApoE-deficient rats; Hypercholesterolemia; Renal sympathetic denervation