Influence of theophylline on both bronchoconstriction and plasma extravasation induced by acetaldehyde in guinea-pigs.
Acetaldehyde administered intravenously at various doses (20, 40 and 80 mg/kg) elicits a dose-dependent increase in intratracheal pressure (ITP) and a proportional rise in histamine blood concentration in anaesthetized guinea-pigs. Similar effects were observed in ovalbumin-sensitized guinea-pigs upon aerosol of acetaldehyde (20 mg/ml) which has been administered at the flow rate of 0.1 ml/min for 2 min. Theophylline (CAS 58-55-9) antagonized both the increase of ITP values and the rise of histamine in the blood caused by acetaldehyde given intravenously (ED50 = 5.8 mg/kg i.v.) or by aerosol (ED50 = 4.9 mg/kg i.v.). Furthermore, in animals where combined treatment with pyrilamine (2 mg/kg i.v.) and captopril (2 mg/kg i.v.) resulted in a remarkable potentiation of the bronchoconstrictor response to acetaldehyde (20 mg/kg i.v.), the administration of theophylline (5 mg/kg i.v.) or of the substance P (SP) receptor antagonist, [D-Pro4, D-Trp7.9] SP 4-11 (10 mg/kg i.v.) reduced the augmented action of acetaldehyde on respiratory airways induced by captopril by more than 50%. Moreover, the bronchoconstriction induced by acetaldehyde (40 mg/kg i.v.) was also associated with a significant increase of extravasation of Evans blue in tracheal tissue. Both these effects of acetaldehyde were inhibited by theophylline (10 mg/kg i.v.), whereas a NK1-TK (neurokinin 1-tachykinin) receptor antagonist (412 micrograms/kg i.v.) reduced (81%; p < 0.001) only the vascular permeability changes caused by acetaldehyde.(ABSTRACT TRUNCATED AT 250 WORDS)
Berti
F
F
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Italy.
Rossoni
G
G
Buschi
A
A
Villa
L M
LM
Trento
F
F
Della Bella
D
D
Bagolan
M
M
D000079:Acetaldehyde / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D005070:Evans Blue; D006168:Guinea Pigs; D006636:Histamine Release / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D013373:Substance P; D005070:Evans Blue; C032682:substance P (4-11); D002216:Captopril; D013806:Theophylline; D000079:Acetaldehyde; D011738:Pyrilamine