Sensory nerve-mediated immediate nasal responses to inspired acrolein.
To investigate the role of sensory C-fiber stimulation and tachykinin release in the immediate nasal responses to the sensory irritant acrolein, the upper respiratory tract of the urethan-anesthetized male Fischer 344 rat was isolated via insertion of an endotracheal tube, and acrolein-laden air [2, 5, 10, or 20 parts/million (ppm)] was drawn continuously through that site at a flow rate of 100 ml/min for 50 min. Uptake of the inert vapor acetone was measured throughout the exposure to assess nasal vascular function. Plasma protein extravasation into nasal tissue and nasal lavage fluid was also assessed via injection of Evans blue dye. At 20 ppm, acrolein induced 1) a twofold increase in acetone uptake, indicative of vasodilation, followed by a progressive decline toward basal levels and 2) increased plasma protein extravasation, as indicated by dye leakage into nasal tissue and nasal lavage. These responses were inhibited by capsaicin pretreatment and the neurokinin type 1 antagonist N-acetyltrifluoromethyl tryptophan benzyl ester and were potentiated by the peptidase inhibitors phosphoramidon and captopril, suggesting that these responses were mediated by tachykinin. At lower exposure concentrations, acrolein was without effect on dye leakage but produced vasodilation, as indicated by increased acetone uptake. The responses at the lower concentrations were inhibited by capsaicin pretreatment, implicating nasal sensory C-fiber involvement, but were not influenced by N-acetyltrifluoromethyl tryptophan benzyl ester, phosphoramidon, or captopril, suggesting the involvement of a mediator other than the tachykinins substance P and neurokinin A.
Morris
J B
JB
Toxicology Program, Department of Pharmaceutical Sciences, University of Connecticut, Storrs 06269-2092, USA. morris@uconnvm.uconn.edu
Stanek
J
J
Gianutsos
G
G
D000096:Acetone / Q000494:pharmacology; D000171:Acrolein / Q000008:administration & dosage / Q000494:pharmacology*; D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D005070:Evans Blue; D007509:Irritants / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009296:Nasal Cavity / Q000502:physiology; D009297:Nasal Mucosa / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects*; D064729:Neurokinin-1 Receptor Antagonists; D009475:Neurons, Afferent / Q000187:drug effects*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D007509:Irritants; D064729:Neurokinin-1 Receptor Antagonists; D011480:Protease Inhibitors; D000096:Acetone; D005070:Evans Blue; D000171:Acrolein; D002211:Capsaicin