Author + information
- 1Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- 2Department of Forensic Medicine, Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, China
- 3Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, China
Anatomical distribution and neural remodeling of renal sympathetic nerve (RSN) and renal ganglion (RG), the important substrates for application of renal sympathetic denervation (RDN), is poorly understood. This study was aimed to three-dimensionally (3D) investigate the anatomy and neural remodeling characteristics of RSN and RG in hypertensive canine and patient.
Renal arteries (RA) were collected from hypertensive and nonhypertensive canines and cadavers. Serial hematoxylin-eosin sections of RA were used for 3D reconstruction and parameters including RSN and RG number, distance, volume and RSN/RA volume ratio were analyzed. Renal tissue norepinephrine of canine and immunoreactivity of tyrosine hydroxylase (TH), substance P and growth-associated protein 43 (GAP 43) in RSN or RG were evaluated.
14 canines and 7 cadavers were included. In canines, the RSN volume (P = 0.001) and RSN/RA volume ratio (P = 0.008), but not mean number (P = 0.82), in proximal were significantly greater than that of distal. The RSN number (26.71±5.68 versus 19.84±5.68, P = 0.02), renal tissue norepinephrine (106. 6±37.6 ng/g versus 65.4±21.7 ng/g, P = 0.027), density of TH (0.235±0.020 versus 0.189±0.044, P = 0.025) and substance P (0.240±0.007 versus 0.187±0.018, P = 0.09) in RSN and GAP43 (41481.8±5757.6 μm2/mm2 versus 17813.0±4557.0 μm2/mm2, P = 0.012) in aortic RG were statistically increased in hypertensive canines. Human RSN was evenly distributed along RA with network pattern. The volume and distance of human RSN and RG were gradually decreased from proximal to distal. There was no significant difference in RSN volume between hypertensive and non-hypertensive patients. The RG volume (72.75±33.43 mm3 versus 37.04±23.95 mm3, P = 0.029), immunoreactivity of TH (0.153±0.014 versus 0.104±0.019, P < 0.0194) in RSN and GAP43 (86612.8±14642.0 μm2/mm2 versus 33469.8±15666.8 μm2/mm2, P < 0.001) in RG were remarkably elevated in hypertensive patients.
These data both suggests that targeting distal part of RA might be an optimal strategy for RDN, and provide potent histopathological evidence of RSN remodeling for continuing application of RDN in hypertension. In future, our human RSN 3D models may benefit for the optimization of RDN devices and ablation parameters.