Sensory Nerve-Mediated Nasal Vasodilatory Response to Inspired Ethyl Acrylate

Abstract

The irritants acrolein, acetaldehyde, and acetic acid induce a rapid sensory nerve-mediated nasal vasodilatory response in the rat. The aim of the current study was to examine acute nasal sensory nerve-mediated acute responses to an irritant ester vapor, ethyl acrylate. For this purpose, the upper respiratory tract of the urethane-anesthetized male F344 rat was isolated by insertion of an endotracheal cannula, and ethyl acrylate-laden air was drawn continuously through that site at a flow rate of 100 ml/min for 50 min. Vascular function was monitored by measuring inert vapor (acetone) uptake throughout the exposure. Nasal flow resistance was also monitored during exposure, and plasma protein extravasation was measured by Evans blue dye leakage. At exposure concentrations of 100 to 400 ppm, ethyl acrylate induced a rapid nasal vasodilatory response, as indicated by increased acetone uptake rates. This response was maintained throughout the exposure. Changes in nasal flow resistance or in Evans blue dye leakage were not observed at these exposure concentrations. The vasodilatory response was diminished in animals pretreated with the sensory nerve toxin capsaicin, providing strong evidence that this response was sensory nerve mediated. Pretreatment with the carboxylesterase inhibitor bis-para-nitro-phenolphospahte at a dose sufficient to inhibit nasal carboxylesterase did not alter the response, suggesting that the parent ester, not the carboxylesterase metabolites, is primarily responsible for the sensory-nerve-mediated vasodilatory responses to this ester.

Immediate sensory nerve-mediated respiratory responses to irritants in healthy and allergic airway-diseased mice

“…These exposure concentrations were estimated to approximate the RD 50 based on pilot studies. Our laboratory's previous studies on the rat indicated that local tissue responses were easily demonstrable at RD 50 of each irritant (26,28,29,39).…”

“…URT acetone vapor uptake was monitored during exposure as a measure of URT perfusion rates by the methods used in our laboratory's previous studies (26,28,31). Briefly, vapor concentrations in chamber air (C in) and in air that had been drawn through the isolated URT (Cex) were measured by gas chromatography as described above.…”

“…The vasodilatory response to every vapor was greatly reduced and/or abolished in animals pretreated with capsaicin, confirming a key role for sensory nerves. The precise mediators involved in this response are not known; however, preliminary studies suggest a role for calcitonin gene-related peptide and nitric oxide (27)(28)(29).…”

“…The aims of the present study were twofold: 1) to characterize the response of the mouse nose to acrolein and acetic acid vapor to allow for comparison with our laboratory's earlier rat studies (26,28,29,39) and 2) to compare responses in healthy and allergic airway-diseased mice. The initial experiments relied on methodologies identical to those used in our previous rat studies to facilitate comparisons.…”

“…Previous studies in our laboratory were aimed at characterizing upper respiratory tract (URT) sensory nerve-mediated responses to inspired irritants in the rat and included measures of afferent reflex responses (changes in breathing pattern) and local tissue responses, including neurogenic edema, airway obstruction, and mucus secretion (26,28,39). (The URT is defined as all portions of the respiratory tract anterior to and including the larynx.)…”