1,8-Cineole induces relaxation in rat and guinea-pig airway smooth muscle

Objectives 1,8-Cineole is a monoterpene with anti-inflammatory, vascular and intestinal smooth muscle relaxant activity. We have evaluated the potential bronchodilatatory activity of this Compound. Methods 1,8-Cineole was tested against carbachol, histamine, K(+) 80 mM and ovalbumin-induced bronchial contractions in Wistar rat or guinea-pig tissues. Some of the guinea-pigs had been previously sensitized with an intramuscular injection of 5% (w/v) ovalbumin/saline Solution. Control animals received 0.3 ml saline. In separate experimental groups the response to 1,8-cineole (1-30 mg/kg), phenoterol (0.05-5 mg/kg) or vehicle (0.3% Tween in saline) was studied. Key findings 1,8-Cineole decreased, in, vivo, rat bronchial resistance with similar efficacy as phenoterol (66.7 +/- 3.2% vs 72.1 +/- 5.3%). On the other hand, the maximal relaxant response to 1,8-cineole in carbachol-precontracted rat tracheas was 85.5 +/- 5.7% (IC50 = 408.9 (328-5196) mu g/ml) compared with 80.2 +/- 4.8% (IC50 = 5.1 (4.3-6.1) mu g/ml) with phenoterol. The addition of 1,8-cineole to gLlinea-pig tracheal rings tonically contracted with K(+) 80 mm induced a concentration-related relaxation. The maximal relaxation elicited by 1,8-cineole was 113.6 +/- 11.7% (IC50 127.0 (115.9-139.2) mu g/ml) compared with 129.7 +/- 14.6% (IC50 0.13 (0.12-0.14) mu g/ml) achieved after phenoterol administration. In addition, the incubation of tracheal rings with 1,8-cineole (100, 300 or 1000 mu g/ml), 15 min before inducing phasic contractions with K(+) 80 mm, decreased the maximal amplitude of the contraction by 31.6 +/- 4.6, 75.7 +/- 2.7 and 92.2 +/- 1.5%, respectively. In another set of experiments, neither the maximal response nor the IC50 for the 1,8-cineole-induced relaxation were different between normal and ovalbumin-sensitized tissues. Moreover, the relaxation of bronchial rings contracted after exposure to 1 mu g/ml ovalbumin occurred at a faster rate in rings pre-incubated with 1,8-cineole when compared with rings pre-incubated with vehicle only (Tween 0.3%). Therefore, in the first minute after the antigen challenge, the tracheal tissue relaxed after the peak contraction by 6.5, 21.4 (P < 0.05 vs control) and 66.9% (P < 0.05 vs control) in the presence of 100, 300 or 1000 mu g/ml 1,8-cineole, respectively. Conclusions 1,8-Cineole relaxed rat and guinea-pig (nonsensitized and ovalbuminsensitized) airway smooth muscle by a nonspecific mechanism.