Occurrence, distribution and possible role of the regulatory peptide endothelin in the nasal mucosa

Abstract

Nasal blood flow is finely regulated by local release of neurotransmitters, neuropeptides and other bioactive molecules acting via paracrine mechanisms. We have investigated the occurrence and distribution in human nasal mucosa of endothelin, a potent vasoconstrictor peptide, by immunocytochemistry and the effect of systemic administration of endothelin-1 on vascular perfusion of rabbit nasal mucosa by laser Doppler flowmetry. Endothelin-like immunoreactivity was demonstrated within vascular endothelial cells in both developing and mature human mucosa. Nasal epithelial cells and some connective tissue cells, presumed to be macrophages, also displayed specific immunostaining. In rabbits injected with endothelin-1, a potent and prolonged nasal vasoconstriction was observed. It is suggested that endothelin released locally may participate in the regulation of nasal blood flow via paracrine mechanisms. Since endothelin has growth-promoting actions on several cell types, it is also tentatively proposed that this regulatory peptide may play a role during development of the nose.

Presence and location of endothelin and endothelin-binding sites in human nasal mucosa under normal and metaplastic conditions

“…Some researchers have demonstrated the presence (Casasco et al 1993) and the production (Mullol et al 1993) of ET in human nasal epithelium. However, as far as we know, no study concerning the difference between normal and metaplastic epithelium has been carried out.…”

“…These agents can regulate the tone and permeability of blood vessels by means of local action through an autocrine/paracrine mechanism (Casasco et al 1993;Riccio et al 1995). Among these substances, the endothelins (ETs) play a prominent role.…”

“…The presence of ET in the endothelium of the nasal vessels has also been demonstrated by immunoreactivity (Ichimura et al 1991;Casasco et al 1993). Nevertheless, little research has been carried out regarding the localization of the ET receptors in the nasal mucosa or the site of ET production (Hemsen and Lundberg 1991;Mullol et al 1993).…”

Endothelin in nasal mucosa: role in nasal function and inflammation

“…In human nasal mucosa, ET was first reported in the endothelial cells of both capacitance and resistance blood vessels [ 12]. Both immunoreactive ET‐1 and endothelin‐converting enzyme (ECE)‐1 are expressed in epithelial and endothelial cells, submucosal glands (in mucous cells and to a greater extent in serous cells), inflammatory cells (macrophages), and blood vessels such as arterioles, small veins and venous sinusoids of human nasal mucosa [ 13–17] ( Table 1). These findings contrast with the distribution of other peptides such as calcitonin gene‐related peptide (CGRP), neuropeptide Y (NPY), gastrin‐releasing peptide (GRP), vasoactive intestinal polypeptide (VIP), substance P (SP), and neurokinin A (NKA), which are mainly present in bundle nerves involved in adrenergic, cholinergic and nonadrenergic, noncholinergic functions [ 18–21].…”

Expression of Endothelin A- and B-receptors in Human Nasal Mucosa

“…In the nose, ET is primarily produced by the airway epithelium and the vascular endothelium (1 -3) and is suggested to play a role in the regulation of vascular tone and permeability by means of local action through autocrine/paracrine mechanisms (1,4). ET is also found in submucosal glands of patients with nasal airway obstruction, and together with functional evidence from lower animal airways, it implies a direct role for ETs in the regulation of nasal secretion (3,5).…”