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




Modulation of the sympathetic nervous system by renal denervation prevents reduction of aortic distensibility in atherosclerosis prone ApoE-deficient rats - Download this document for free, or read online. Document in PDF available to download.

Journal of Translational Medicine

, 14:167

Cardiovascular, Metabolic andLipoprotein Translation

Abstract

BackgroundApolipoprotein 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.

MethodsNormotensive, 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.

ResultsAfter 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.

ConclusionApoE-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.

KeywordsApoE-deficient rats Hypercholesterolemia Aortic distensibility Renal sympathetic denervation AbbreviationsAFatrial fibrillation

ApoEapolipoprotein E-deficient

BPblood pressure

EDend diastole

ESend systole

eNOSendothelial nitric oxide synthase

GAPDHglyceraldehyd-3-phosphate-dehydrogenase

GPTglutamat-pyruvat-transaminase

GOTglutamat-oxalacetat-transaminase

HDLhigh-density lipoprotein

HPLChigh pressure liquid chromatography

HRheart rate

ICAM-intercellular adhesion molecule

IL1βinterleukin 1 beta

LDLlow-density lipoprotein

LVESVleft ventricular end-systolic volume

LVEDVleft ventricular end-diastolic volume

MNCsmononuclear cells

MRImagnetic resonance imaging

NEnorepinephrine

NOnitric oxide

PPpulse pressure

RAASrenin-angiotensin-aldosterone-system

RDNrenal denervation

ROSreactive oxygen species

SDSprague–Dawley

SNSsympathetic nervous system

TNFαtumor necrosis factor alpha

VCAM-1vascular cell adhesion molecule-1

Electronic supplementary materialThe online version of this article doi:10.1186-s12967-016-0914-9 contains supplementary material, which is available to authorized users.

Download fulltext PDF



Author: Mathias Hohl - Dominik Linz - Peter Fries - Andreas Müller - Jonas Stroeder - Daniel Urban - Thimoteus Speer - Jürgen Ge

Source: https://link.springer.com/







Related documents