INFLUENCE OF THEOPHYLLINE ON BOTH BRONCHOCONSTRICTION AND PLASMA EXTRAVASATION INDUCED BY ACETALDEHYDE IN GUINEA-PIGS

Acetaldehyde administered intravenously at various doses (20, 40 and 8 0 mg/kg) elicits a dose-dependent increase in intratracheal pressure ( ITP) and a proportional rise in histamine blood concentration in anaes thetized guinea-pigs. Similar effects were observed in ovalbumin-sensi tized guinea-pigs upon aerosol of acetaldehyde (20 mg/ml) which has be en 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 ris e 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.). Furt hermore, in animals where combined treatment with pyrilamine (2 mg/kg i. v.) and captopril (2 mg/kg iv.) resulted in a remarkable potentiati on of the bronchoconstrictor response to acetaldehyde (20 mg/kg i. v.) , the administration of theophylline (5 mg/kg i. v. ) or of the substa nce 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 airway s induced by captopril by more than 50 %. Moreover, the bronchoconstri ction induced by acetaldehyde (40 mg/kg i. v.) was also associated wit h a significant increase of extravasation of Evans blue in tracheal ti ssue. Both these effects of acetaldehyde were inhibited by theophyllin e (10 mg/kg iv.), whereas a NK1-TK (neurokinin 1-tachykinin) receptor antagonist (412 mug/kg i. v. ) reduced (81 %; p < 0.001) only the vasc ular permeability changes caused by acetaldehyde. In conclusion, the p rotecting activity observed with theophylline against acetaldehyde act ions in guinea-pigs, takes place at doses inferior to those necessary to antagonize acetylcholine-induced bronchoconstriction and appears to involve the inhibition of histamine secretion and to control the acti vation of sensory nerve endings and tachykinin release.