Sensory nerve-mediated nasal vasodilatory response to inspired ethyl acrylate.
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.
Toxicology Program, Department of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut 06269-3092, USA. morris@uconnvm.uconn.edu
John B
JB
Morris
D000096:Acetone / Q000494:pharmacology; D000179:Acrylates / Q000633:toxicity*; D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007509:Irritants / Q000633:toxicity*; D008297:Male; D009296:Nasal Cavity / Q000098:blood supply* / Q000294:innervation; D009475:Neurons, Afferent / Q000502:physiology*; D009596:Nitrophenols / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D014664:Vasodilation / Q000187:drug effects*
D000179:Acrylates; D004791:Enzyme Inhibitors; D007509:Irritants; D009596:Nitrophenols; D000096:Acetone; C002887:bis(4-nitrophenyl)phosphate; C040833:ethyl acrylate; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D002211:Capsaicin