title: 1,8-Cineole induces relaxation in rat and guinea-pig airway smooth muscle.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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) microg/ml) compared with 80.2 +/- 4.8% (IC50 = 5.1 (4.3-6.1) microg/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) microg/ml) compared with 129.7 +/- 14.6% (IC50 0.13 (0.12-0.14) microg/ml) achieved after phenoterol administration. In addition, the incubation of tracheal rings with 1,8-cineole (100, 300 or 1000 microg/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 microg/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 microg/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.
authors.affiliation: Institute for Biomedical Science, Veterinary College, State University of Ceará, Fortaleza, Ceará, Brazil. nilberto.nascimento@gmail.com
authors.forename: Nilberto Robson Falcão
authors.initials: NR
authors.lastname: Nascimento
authors.forename: Rafael Mohana De Carvalho
authors.initials: RM
authors.lastname: Refosco
authors.forename: Elainne Cristine Félix
authors.initials: EC
authors.lastname: Vasconcelos
authors.forename: Marta Regina
authors.initials: MR
authors.lastname: Kerntopf
authors.forename: Cláudia Ferreira
authors.initials: CF
authors.lastname: Santos
authors.forename: Francisco José Arnaud
authors.initials: FJ
authors.lastname: Batista
authors.forename: Clauber Mota
authors.initials: CM
authors.lastname: De Sousa
authors.forename: Manassés Claudino
authors.initials: MC
authors.lastname: Fonteles
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003511:Cyclohexanols / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000077591:Eucalyptol; D005260:Female; D005280:Fenoterol / Q000008:administration & dosage / Q000494:pharmacology; D006168:Guinea Pigs; D020128:Inhibitory Concentration 50; D008297:Male; D039821:Monoterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D010047:Ovalbumin; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
chemical_list: D001993:Bronchodilator Agents; D003511:Cyclohexanols; D039821:Monoterpenes; D005280:Fenoterol; D010047:Ovalbumin; D000077591:Eucalyptol