Influence of acetaldehyde on airway resistance and plasma exudation in the guinea-pig
Berti, F.; Rossoni, G.; Della Bella, D.; Trento, F.; Bernareggi, M.; Robuschi, M.
Arzneimittel-Forschung 44(12): 1342-1346
1994
ISSN/ISBN: 0004-4172 PMID: 7531441 Document Number: 432731
In anaesthetized ventilated guinea-pigs, 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 lt 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 lt 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 lt 0. 01) and Evans blue extravasation (215%; p lt 0.01) induced by acetaldehyde (20 mg/kg i.v.) in normal guinea-pigs. Furthermore, treatment with CP-96,345, a selective tachykinin NK-1-receptor antagonist, only prevents plasma extravasation in lower tracheal tissue (82% inhibition; p lt 0.01) without affecting the bronchoconstriction caused by acetaldehyde (40 mg/ kg i.v.). Pyrilamine (2 mg/kg iv.), nimesulide (0.5 mg/kg i.v.) and theophylline (10 mg/kg i.v.), with different mechanisms, display a significant protective activity against the bronchoconstriction induced by acetaldehyde (40 mg/kg i.v.) and inhibit plasma extravasation in the range of 50% (p lt 0.01). These data suggest that the effects of acetaldehyde in respiratory smooth muscle and microvascular permeability of guinea pig airways may be the result of an interaction between substance P-like material and histamine released by the aldehyde. Moreover, these findings may also have implications in respiratory disease, particularly in asthmatic patients with reduced aldehyde-dehydrogenase activity: in these patients repeated alcohol intake may elicit bronchoconstriction and haemodynamic alterations.