Nasal response to substance P and methacholine in subjects with and without allergic rhinitis

Abstract

We compared the rise in nasal airway resistance (NAR) provoked by topical application of substance P (SP) and of methacholine (MCH) in seventeen patients suffering from rhinitis and fourteen control subjects. Challenges with SP or MCH were separated by a week or more. NAR was measured by posterior rhinomanometry before and 10 min after intranasal administration of SP (10-40 nmol) or MCH (3-12 mumol). The two groups of subjects had similar baseline levels of NAR and similar small responses to buffered saline. Substance P but not MCH provoked cutaneous flushing in all subjects. Both SP and MCH provoked a significantly greater increase in NAR in patients suffering from rhinitis than in control subjects. The increase in NAR was dose-dependent, and on a molar basis, SP was 375-500-fold more potent than MCH. Pretreatment with 200 micrograms of a topically active anticholinergic agent, oxytropium bromide, prevented the rise in NAR caused by 12 mumol of MCH but not that caused by 40 nmol of SP in six patients suffering from rhinitis. We conclude that SP is absorbed across the nasal mucosa and causes cutaneous vasodilation, that MCH and SP cause a greater rise in NAR in patients suffering from rhinitis than in control subjects, that SP is about 500-fold more potent than MCH in increasing NAR, and that the rise in NAR caused by SP is not mediated by postganglionic parasympathetic mechanisms.

Modulation by theophylline and enprofylline of the excitatory non-cholinergic transmission in guinea-pig bronchi

“…Their neuromediators are the neuropeptides substance P, neurokinin A and calcitonin gene-related peptide, capable of causing neurogenic bronchoconstriction, mucosecretion, vasodilatation and increase in microvascular permeability, leading to plasma exsudation and inflammatory cell infiltrate in the airways in animals [14,17,[22][23][24]. In humans, although no effect of exogenous tachykinins is observed in the airways of healthy subjects, airway obstruction is induced by inhalation or nebulization of tachykinins in patients with allergic asthma [25] or rhinitis [15,26). SP-induced nasal obstruction is associated with influx of albumin, protein and inflammatory cells, polymorphonuclear cells and eosinophils, in the nasal lavage fluid (15,27].…”

Influences of Allergic Rhinitis on Sleep

“…41 Both neutrophils and bradykinin levels in nasal lavage fluid were significantly greater (P Ͻ 0.05), both before and after sleep, in the subjects with OSA, suggesting that these patients had some degree of nasal inflammation, which could have contributed to their sleep disorder. 41 Unstudied with regard to their impact on sleep but implicated as a cause of nasal congestion are neuropeptides such as substance P. 42,43 Nasal challenge with substance P produced a dose-dependent increase in nasal airway resistance in AR patients (P Ͻ 0.01) but not control subjects. 42 Furthermore, substance P has been shown to increase REM latency and to have an arousal effect.…”

“…41 Unstudied with regard to their impact on sleep but implicated as a cause of nasal congestion are neuropeptides such as substance P. 42,43 Nasal challenge with substance P produced a dose-dependent increase in nasal airway resistance in AR patients (P Ͻ 0.01) but not control subjects. 42 Furthermore, substance P has been shown to increase REM latency and to have an arousal effect. 44…”

Allergic Rhinitis: Broader Disease Effects and Implications for Management

“…56 These neuropeptides can induce vasodilation and contribute to rhinorrhea and congestion. 57,58 In the arterioles, most of the receptors are for CGRP, which causes vasodilation, or for neuropeptide Y, which induces vasoconstriction. SP is the only neuropeptide for which both fibers and receptors have been localized to the nasal epithelium.…”

“…In addition to the identification of these neuropeptides in the nasal mucosa, incubation of nasal biopsy specimens of perennial rhinitics and nonallergic rhinitics with substance P (SP) or mite allergen resulted in significant increases in mRNA for IL‐1β, IL‐2, IL‐3, IL‐4, IL‐5, IL‐6, tissue necrosis factor (TNF)‐α, and interferon (IFN)‐γ in specimens from the allergic subjects but not nonallergic controls, supporting the importance of these peptides in amplifying allergic inflammation 56 . These neuropeptides can induce vasodilation and contribute to rhinorrhea and congestion 57,58 . In the arterioles, most of the receptors are for CGRP, which causes vasodilation, or for neuropeptide Y, which induces vasoconstriction.…”