GABA-immunoreactivity in Neuroepithelial Bodies of Spontaneously Hypertensive Rats

Abstract

Neuroepithelial bodies (NEBs) are complex sensory receptors dispersed throughout the intrapulmonary airways. They are composed of pulmonary neuroendocrine cells (PNECs) which have a large amount of dense-core vesicles containing calcitonin gene-related peptide (CGRP), serotonin (5HT), substance P (SP) and δ-aminobutyric acid (GABA). NEBs are densely innervated by vagal sensory terminals, dorsal root afferents and intrinsic motor fibres. Their location, neurochemical composition and dense innervation make NEBs a key component for the regulation of lung homeostasis. Pulmonary arterial hypertension is a rare disease characterized by morphological alterations in the microcirculation of the lungs causing a wide array of complications and high mortality. Spontaneously hypertensive rats (SHRs) are a common model for essential hypertension, that may develop secondary pulmonary hypertension and thus can be used as an animal model to study pulmonary pressure changes. The present study focuses on the immunohistochemical demonstration of GABA in the NEBs and its potential role in the regulation of the pulmonary pressure. Two groups of SHRs were used and age-matched normotensive Wistar Kyoto (WKY) rats served as controls. We found single PNECs and clusters of GABA-immunoreactive cells protruding into the lumen of the intrapulmonary airways in all examined groups of SHRs and in the normotensive WKY rats. However, the expressional levels statistically differed within the two age groups of SHRs and the controls. Specifically, the NEBs and PNECs in 1-month-old SHRs and particularly in 3-month-old SHRs showed more intense GABA-immunostaining compared to the WKY rats. In conclusion, NEBs and PNECs react to the alterations of the pulmonary pressure homeostasis by an increased GABA expression as a preventive or reactive regulation mechanism against developing pulmonary hypertension.