Sensory-Nerve-Mediated Nasal Vasodilatory Response to Inspired Acetaldehyde and Acetic Acid Vapors

Abstract

This study was designed to characterize the acute nasal vasodilatory responses to the sensory irritants acetaldehyde and acetic acid. For this purpose, the upper respiratory tract of the urethane-anesthetized male F344 rat was isolated by insertion of an endotracheal cannula, and irritant-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. Both acetaldehyde and acetic acid induced an immediate concentration-dependent vasodilation as indicated by increased steady-state acetone uptake rates. This response was observed at exposure concentrations of 25 ppm or 130 ppm or higher for acetaldehyde or acetic acid, respectively. The response to either vapor was significantly diminished in rats pretreated with the sensory nerve toxin capsaicin (50 mg/kg, 7 days prior to exposure), providing evidence that sensory nerves play a role in the response. Acetaldehyde is metabolized by aldehyde dehydrogenase to acetic acid. Pretreatment with the aldehyde dehydrogenase inhibitor cyanamide (10 mg/kg, 1 h prior to exposure) reduced the vasodilatory response to 200 ppm but not to 50 ppm acetaldehyde. These results suggest that formation of acetic acid is important in the sensory nerve-mediated vasodilatory response to high, but perhaps not to low, concentrations of acetaldehyde.

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

“…Air samples were drawn from the nose-only chamber or plethysmograph during exposure to determine exposure concentration using methods employed in our laboratory's previous studies (28,29,39). For acrolein or acetone analysis, air was drawn through a gas-sampling valve attached to a gas chromatograph (model 3600, Varian, Sugar Land, TX) with flame ionization detection.…”

“…These studies have examined the effects of two reactive electrophilic vapors, acrolein and ethyl acrylate, and two vapors for which tissue acidification is believed to be important, acetic acid vapor and acetaldehyde. [Acetaldehyde is metabolized in nasal tissues to acetic acid via aldehyde dehydrogenase, and this is believed to be a critical step in its nasal toxicity (24,38,39).] Of the responses measured, the most sensitive for all four vapors was vasodilation.…”

“…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.…”

“…Before exposure, animals were injected with Evans blue, a dye that binds to albumin. Dye content in nasal tissues and nasal airway lavage fluid (obtained immediately after exposure) provides a measure of plasma protein leakage/secretion into these compartments (28,29,31,39). The same technique was used to quantitate URT uptake efficiency of acrolein and acetic acid vapors.…”

“…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.)…”