Interventions for hypertension and stroke

Histological examination of renal nerve distribution, density, and function in humans

EuroIntervention 2023;19:612-620. DOI: 10.4244/EIJ-D-23-00264

Helge Struthoff
Helge Struthoff1, MD; Lucas Lauder1; Mathias Hohl1, PhD; Alexander Hermens1, PhD; Abraham Rami Tzafriri2, PhD; Elazer R. Edelman3,4, MD, PhD; Michael Kunz1, MD; Michael Böhm1, MD; Thomas Tschernig5, MD; Felix Mahfoud1, MD, MA
1. Klinik für Innere Medizin III – Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes and Saarland University, Homburg, Germany; 2. CBSET, Inc., Lexington, MA, USA; 3. IMES, Massachusetts Institute of Technology, Cambridge, MA, USA; 4. Division of Cardiovascular Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; 5. Institute for Anatomy and Cell Biology, Faculty of Medicine, Saarland University, Homburg, Germany

Background: Renal denervation is optimised when guided by knowledge of nerve distribution.

Aims: We aimed to assess sympathetic nerve distribution along the renal arteries, especially in post-bifurcation vessel segments.

Methods: Renal arteries and surrounding tissue from 10 body donors were collected and examined histologically. Immunohistochemical staining was used to analyse nerve distribution and to identify afferent and efferent sympathetic nerves.

Results: A total of 6,781 nerves surrounding 18 renal arteries were evaluated. The mean lumen-nerve distance of the left renal artery (2.32±1.95 mm) was slightly greater than the right (2.29±2.03 mm; p=0.161); this varied across the arteries’ courses: 3.7±2.3 mm in proximal segments, 2.5±2.0 mm in middle segments, 1.9±1.6 mm in distal prebifurcation segments and 1.3±1.0 mm in post-bifurcation segments (p<0.001). The number of nerves per quadrant was highest in the proximal segments (13.7±18.6), followed by the middle (9.7±7.9), distal prebifurcation (8.0±7.6), and distal post-bifurcation (4.3±4.0) segments (p<0.001). Circumferentially, the number of nerves was highest in the superior (7.8±9.4) and the ventral (7.6±13.1) quadrants (p=0.638). The mean tyrosine hydroxylase (TH) to calcitonin gene-related peptide (CGRP) ratio increased from proximal (37.5±33.5) to distal (72.0±7.2 in the post-bifurcation segments; p<0.001). Thirty-eight neuroganglia were identified along 14 (78%) renal arteries.

Conclusions: Nerves converge to the renal arteries’ lumen in the distal segments and along branches, resulting in the lowest number of nerves per quadrant and the shortest lumen-nerve distance in the distal post-bifurcation segments. Efferent nerves occur predominantly, and the ratio of efferent to afferent nerves continues to increase in the vessels’ course.

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