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

• Published in: Journal of pharmacy and pharmacology 2009-03, Vol.61 (3), p.361-366
• Main Authors: Nascimento, Nilberto Robson Falcão, Refosco, Rafael Mohana De Carvalho, Vasconcelos, Elainne Cristine Félix, Kerntopf, Marta Regina, Santos, Cláudia Ferreira, Batista, Francisco José Arnaud, De Sousa, Clauber Mota, Fonteles, Manassés Claudino
• Format: Article
• Language: English
• Subjects: 1,8‐cineole; 8-cineole; airway smooth muscle; Animals; Bronchi - drug effects; Bronchi - metabolism; bronchodilatatory activity; Bronchodilator Agents - administration & dosage; Bronchodilator Agents - pharmacology; Cyclohexanols - administration & dosage; Cyclohexanols - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Fenoterol - administration & dosage; Fenoterol - pharmacology; Guinea Pigs; Inhibitory Concentration 50; Male; Monoterpenes - administration & dosage; Monoterpenes - pharmacology; Muscle Relaxation - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - metabolism; Ovalbumin; phenoterol; Rats; Rats, Wistar; Trachea - drug effects; Trachea - metabolism
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1211/jpp.61.03.0011

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) μg/ml) compared with 80.2 ± 4.8% (IC50 = 5.1 (4.3–6.1) μg/ml) with phenoterol. The addition of 1,8‐cineole to guinea‐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) μg/ml) compared with 129.7 ± 14.6% (IC50 0.13 (0.12–0.14) μg/ml) achieved after phenoterol administration. In addition, the incubation of tracheal rings with 1,8‐cineole (100, 300 or 1000 μg/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 μg/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 μg/ml 1,8‐cineole, respectively. Conclusions 1,8‐Cineole relaxed rat and guinea‐pig (nonsensitized and ovalbumin‐sensitized) airway smooth muscle by a nonspecific mechanism.