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Quantification of Neuroepithelial Bodies and Their Innervation in Fawn-Hooded and Wistar Rat Lungs

Department of Biomedical Sciences, Laboratory of Cell Biology and Histology, University of Antwerp—RUCA
Antwerp, Belgium; and Autonomic Neuroscience Institute, Royal Free and University College Medical School
London, United Kingdom

Address correspondence to: Dirk Adriaensen, Laboratory of Cell Biology and Histology, University of Antwerp—RUCA, Groenenborgerlaan 171, B-2020 Antwerp, Belgium. E-mail: dadria{at}ruca.ua.ac.be

The Fawn-Hooded rat (FHR), a model for primary pulmonary hypertension, shows an unexplained hypersensitivity to airway hypoxia. Because pulmonary neuroepithelial bodies (NEBs) appear to express a functional oxygen-sensing mechanism and an extensive sensory innervation, possible changes in this system should be taken into consideration. In the present study a comparative analysis of NEBs and their selective innervation was performed in FHRs and Wistar control rats. In both rat strains, the number of NEBs was estimated to be around 3,500, 40% of which were innervated by vagal sensory calbindin D28k-immunoreactive (IR) nerve endings and 50% by spinal sensory calcitonin gene-related peptide (CGRP)-IR nerve terminals. The number of intrinsic pulmonary nitrergic neurons and the percentage of pulmonary NEBs revealing a nitrergic innervation were highly significantly lower in FHRs. In both FHRs and Wistar rats, a remarkable morphologic interaction was observed between the intrinsic nitrergic and the CGRP-IR sensory population contacting NEBs. Our findings suggest a possible link between the hypersensitivity to airway hypoxia observed in FHRs and a reduced intrinsic pulmonary nitrergic innervation, possibly via the interaction with pulmonary NEBs and their spinal sensory CGRP-IR innervation.

Abbreviations: calbindin D28k, CB • calcitonin gene-related peptide, CGRP • diffuse neuroendocrine system, DNES • Fawn-Hooded rat, FHR • immunoreactive/immunoreactivity, IR • neuroepithelial bodies, NEBs • neuronal nitric oxide synthase, nNOS • nitric oxide, NO • overnight, ON • phosphate-buffered saline, PBS • protein gene product 9.5, PGP9.5 • primary pulmonary hypertension, PPH • substance P, SP • tyrosine hydroxylase, TH • tyramide signal amplification, TSA • vesicular acetylcholine transporter, VAChT • vasoactive intestinal polypeptide, VIP

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