Influence of acetaldehyde on airway resistance and plasma exudation in the guinea-pig.
In anaesthetized ventilated guinea-pig, acetaldehyde (CAS 75-07-0) (40-80 mg/kg i.v.) elicits a dose-dependent increase in intratracheal pressure accompanied by an increase in circulating histamine. When acetaldehyde is injected repeatedly at 15 min intervals in capsaicin-desensitized animals, it already loses its activity at the second administration (50% reduction; p < 0.01); this does not happen in control animals. This phenomenon is even more marked when acetaldehyde is given at the dose of 80 mg/kg i.v., since at the third injection both the bronchoconstriction and the increase in blood histamine are almost completely reduced to baseline values. The increase in intratracheal pressure caused by acetaldehyde (20, 40, 80 mg/kg i.v.) is associated with a dose related increase in microvascular permeability and leakage of protein-bound Evans blue in lower tracheal tissue. This event and the bronchoconstrictor response caused by acetaldehyde (40 mg/kg i.v.) are 87% and 35% inhibited, respectively, (p < 0.01) in tachykinin-depleated animals. On the contrary, thiorphan (2 mg/kg i.v.) remarkably potentiates both the rise in intratracheal pressure (110%; p < 0.01) and Evans blue extravasation (215%; p < 0.01) induced by acetaldehyde (20 mg/kg i.v.) in normal guinea-pigs. Furthermore, treatment with CP-96,345, a selective tachykinin NK1-receptor antagonist, only prevents plasma extravasation in lower tracheal tissue (82% inhibition; p < 0.01) without affecting the bronchoconstriction caused by acetaldehyde (40 mg/kg i.v.).(ABSTRACT TRUNCATED AT 250 WORDS)
Berti
F
F
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Italy.
Rossoni
G
G
Della Bella
D
D
Trento
F
F
Bernareggi
M
M
Robuschi
M
M
D000079:Acetaldehyde / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D012132:Respiratory Muscles / Q000187:drug effects
D001713:Biphenyl Compounds; D006993:Hypnotics and Sedatives; D000079:Acetaldehyde; D002211:Capsaicin; C066892:CP 96345