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

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, 8weeks 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 8weeks. 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 8weeks, ApoE/-sham demonstrated a 58% decrease in aortic distensibility when compared with SD-sham (0.0051±0.0011 vs. 0.0126±0.00231/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±8.4pg/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.