Abstract 20189: Renal Denervation With Neuron Targeted Nanoparticles Attenuates the Hypertension Associated With Obesity

Abstract

Introduction: Obesity is associated with hypertension and increased renal sympathetic nervous activity, Our recent study indicated that autonomic denervation could be induced by nanoparticles.In addition, non-toxic fragment of tetanus toxin, known as tetanus toxin C fragment(TTC), which demonstrates extremely high affinity binding to the surfaces of neurons. Hypothesis: This study was to test the hypothesis that renal denervation with TTC-conjugated nanoparticles could attenuate hypertension associated with obesity . Methods: TTC-conjugated nanoparticles and neurotoxic agent (N-isopropylacrylamide monomer) were synthesized. We determined the hemodynamic responses to a high-fat diet in control (n = 6) and renal-denervated by nanoparticles (n = 8) chronically instrumented dogs. After a control period of 7 days, dogs were placed on a high-fat diet for 5 weeks. a modified balloon catheter will be advanced in the target renal artery segment to allow nanoparticles permeating into vascular wall, after that the moving of nanoparticles will be guided by outside magnetic filed towards renal sympathetic nerve.Blood pressure(BP),heart rate variability (HRV),serum norepinephrine (NE) were measured. Pathological examinations were performed on all retrieved samples. Results: In response to a high-fat diet, body weight increased from 17.6 ± 2.4 to 24.8 ± 1.8 kg in the control group. Heart rate increased from 92 ± 6 to 118 ± 10 beats per minute in the control group. BP increased significantly from 105 ± 5 to 139 ± 4 mm Hg in the control group. In contrast, 5 weeks of a high-fat diet in the renal denervation group did not significantly increase body weight(which went from 18.3 ± 2.5 to 19 ± 2.1 mm Hg), Heart rate (which went from 87 ± 3 to 89 ± 6 mm Hg) and BP (which went from 107 ± 3 to 109 ± 6 mm Hg). sympathetic indices of HRV, serum NE, renal sympathetic activity and the expression of c-fos protein in renal sympathetic nerve was significantly lower in the renal denervation group. A histological examination revealed the disruption of nerve fibers, necrosis of Schwann cells and neurons, and apparent denervation in denervation group. Conclusions: Our results indicate that Renal denervation by TTC-conjugated nanoparticles could attenuate hypertension associated with obesity.