Sensory-nerve-mediated nasal vasodilatory response to inspired acetaldehyde and acetic acid vapors.
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.
Stanek
J
J
Toxicology Program, Box U-92, Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269-2092, USA.
Symanowicz
P T
PT
Olsen
J E
JE
Gianutsos
G
G
Morris
J B
JB
D000079:Acetaldehyde / Q000737:chemistry / Q000633:toxicity*; D019342:Acetic Acid / Q000737:chemistry / Q000633:toxicity*; D000280:Administration, Inhalation; D000403:Airway Resistance / Q000187:drug effects; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors; D000818:Animals; D003484:Cyanamide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009296:Nasal Cavity / Q000098:blood supply* / Q000294:innervation; D009297:Nasal Mucosa / Q000098:blood supply / Q000294:innervation; D009300:Nasal Septum / Q000098:blood supply / Q000294:innervation; D009475:Neurons, Afferent / Q000502:physiology*; D010991:Plethysmography; D051381:Rats; D011916:Rats, Inbred F344; D014664:Vasodilation / Q000187:drug effects*; D014835:Volatilization
D004791:Enzyme Inhibitors; D003484:Cyanamide; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde; D019342:Acetic Acid