Sympathetic and parasympathetic interaction in vascular and secretory control of the nasal mucosa in anaesthetized dogs

Abstract

In dogs anaesthetized with pentobarbitone, electrical stimulation of the parasympathetic nerve fibres to the nasal mucosa evoked frequency dependent increases in both nasal arterial blood flow and nasal secretion. Blood flow was measured using a transonic flow probe placed around the artery. Sympathetic nerve stimulation for 3 min at 10 Hz evoked significant and prolonged (> 30 min) attenuation of the vasodilator and secretory responses to subsequent parasympathetic stimulation. Intravenous and intranasal administration of the neuropeptide Y (NPY) analogue N‐acetyl [Leu28,Leu31] NPY 24–36, a selective NPY Y2 receptor agonist (20 nmol kg−1), significantly attenuated both vasodilator and secretory effects of subsequent parasympathetic nerve stimulation. When given intravenously, the inhibitory effect of this Y2 receptor agonist on vascular and secretory effects of parasympathetic nerve stimulation was rapid in onset (5 min) and lasted for more than 60 min. The modulatory effect of the Y2 receptor agonist was also seen with intranasal administration, but was slower in onset (15 min), and lasted less than 45 min. The effects of the intranasal pretreatment with the Y2 receptor agonist were significantly prolonged in the presence of the endopeptidase inhibitor phosphoramidon (10 nm). Atropine pretreatment did not significantly reduce the change in vascular conductance evoked by parasympathetic nerve stimulation. Subsequent pretreatment with the NPY Y2 receptor agonist N‐acetyl [Leu28,Leu31] NPY 24–36 reduced the stimulation induced increase in conductance by 30%. Nasal secretion was reduced by 70% following pretreatment with atropine and a further 30% by pretreatment with the NPY Y2 receptor agonist. Dose dependent vasodilator and secretory effects of local intra‐arterial infusion of acetylcholine and vasoactive intestinal peptide were not modified by the NPY Y2 agonist. Total protein and albumin concentration were measured in nasal lavage fluid collected after nerve stimulation. Atropine pretreatment increased the percentage of the total protein that was albumin in nasal lavage fluid. Neither sympathetic nerve stimulation nor Y2 receptor agonist pretreatment further modified the albumin exudation (a marker of vascular permeability) in nasal fluid lavage collected after parasympathetic nerve stimulation. We propose that sympathetic nerve stimulation releases NPY, which acts on Y2 receptors, probably located on parasympathetic nerve endings, to attenuate both vasodilatation and nasal secretion evoked by subsequent parasympathetic nerve stimulation. This effect is also observed after pretreatment with the Y2‐selective NPY analogue N‐acetyl [Leu28,Leu31] NPY 24–36.

The role of the nervous system in rhinitis

“…21 These neuropeptides have many functions in the nasal airways, including glandular discharge, vasodilatation, and sinusoidal engorgement. [51][52][53] Korsgren et al 54,55 have identified another neuropeptide, secretoneurin, on cholinergic nerves, as well as adrenergic and sensory nerves, in the human nasal mucosa. Secretoneurin has multiple leukocyte-trafficking effects and is a potent angiogenesis factor.…”

Neurology of allergic inflammation and rhinitis

“…The opposing actions of these systems likely determine levels of end organ function in the nose [1,[21][22][23][24][25][26][27][28][29][30]. Postganglionic nerves might also interact prejunctionally on adjacent autonomic nerve endings to modulate neurotransmitter release [1,23].…”

“…Thus, the chemically defined nerve fiber subtypes described in animals are present in the human nasal mucosa. Moreover, NPY and norepinephrine mediate vasoconstriction, while VIP, NO, and acetylcholine mediate vasodilatation and/or mucus secretion in the nose in all species studied, including humans [1,[21][22][23][24][25][26][27][28][29][30].…”

“…Neurotransmitters associated with parasympathetic nerves innervating the nose include acetylcholine, vasoactive intestinal peptide (VIP and related peptides), neuropeptide Y, nitric oxide (NO, synthesized from arginine by the neuronal isoform of NO synthase), enkephalin, and somatostatin. Neurotransmitters associated with sympathetic nerves innervating the nasal mucosa include norepinephrine, neuropeptide Y and somatostatin [21][22][23][24][25].…”

Influence of TASP‐V, a novel neuropeptide Y (NPY) Y2 agonist, on nasal and bronchial responses evoked by histamine in anaesthetized pigs and in humans

“…Recent observations obtained from in vivo experiments in dogs suggest that intranasal pretreatment with a Y 2 -receptor agonist markedly reduced the mucous production evoked by parasympathetic nerve stimulation (Revington et al, 1997). The duration of this eect was signi®cantly prolonged after pretreatment with the endopeptidase inhibitor phosphoramidon.…”