Pneumologie 2015; 69 - A41
DOI: 10.1055/s-0035-1556633

Innervation of pulmonary trunk in mice

A Rafiq 1, T Papadakis 1, M Bodenbenner-Türich 1, W Kummer 1
  • 1Institute for Anatomy and Cell Biology, UGMLC, DZL, Justus-Liebig-University Gießen

The innervation of pulmonary trunk and main pulmonary arteries appears to play an important role in the pathogenesis of pulmonary artery hypertension (PAH). Recently, it has been shown in First-in-Man studies, that denervation proximal to the bifurcation causes normalization of pulmonary artery pressure in patients not responding to classical therapy (Chen et al., J Am Coll Cardiol, 2013; 62(12):1092 – 1100). In rats, pulmonary trunk remodeling induced by hypobaric hypoxia is suppressed in sympathectomized animals (McKenzie JC, Klein RM. J Auton Nerv Syst. 10(2):199 – 203, 1984). The mechanisms underlying this effect are still unclear.

Here we aimed to investigate the extent and precise neurochemical characteristics of pulmonary trunk and artery innervation in vascular whole mounts and sections using wild type (C57Bl/6N) and transgenic reporter mouse strains demonstrating general autonomic (Tg (Chrna3-EGFP) BZ135Gsat) and cholinergic (ChAT BAC-eGFP) nerve fibers. Antibodies were directed against the catecholamine synthesizing enzyme tyrosine hydroxylase (TH), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP; predominantly in sensory neurons) and vasoactive intestinal peptide (VIP).

Interestingly, only the pulmonary trunk is densely innervated while the bifurcation and main pulmonary arteries lack innervation. At least three neurochemical types of axons were distinguished: Noradrenergic with NPY (presumably sympathetic), CGRP-immunoreactive (presumably sensory), and VIP-immunoreactive (presumably parasympathetic). Rank order of frequency is TH/NPY > CGRP >>> VIP. Cholinergic nerve fibers are absent in the pulmonary trunk.

In conclusion, the pulmonary trunk receives a specific autonomic and sensory innervation. The spatial restriction to the trunk matches the clinical data where nerve ablation at the pulmonary arteries was ineffective in PAH patients. We propose that trunk innervation plays an important role in development of PAH by regulating compliance and triggering remodeling.

*Presenting author