Abstract
1. 1,8-Cineole is a terpenoid constituent of essential oils with anti-inflammatory properties. It reduces the neural excitability, functions as an antinociceptive agent and has myorelaxant actions in guinea-pig airways. The aim of the present study was to investigate the mechanism underlying the myorelaxant effects of 1,8-cineole in guinea-pig isolated trachea from either naïve guinea-pigs or ovalbumin (OVA)-sensitized animals subjected to antigenic challenge. 2. Isometric recordings were made of the tone of isolated tracheal rings. Rings with an intact epithelium relaxed beyond basal tone in the presence of 1,8-cineole (6.5 x 10(-6) to 2 x 10(-2) mol/L) in a concentration-dependent manner (P < 0.001, anova) with a pD(2) value of 2.23 (95% confidence interval 2.10-2.37). Removal of the epithelium or pretreatment of intact tissue for 15 min with 50 micromol/L N(G)-nitro-l-arginine methyl ester, 5 mmol/L tetraethylammonium, 0.5 micromol/L tetrodotoxin or 5 micromol/L propranolol did not alter the potency (pD(2)) or the maximal myorelaxant effect (E(max)) of 1,8-cineole. 3. 1,8-Cineole also significantly decreased the Schultz-Dale contraction induced by OVA, mainly in preparations from OVA-sensitized animals submitted to antigen challenge. 1,8-Cineole decreased tracheal hyperresponsiveness to KCl and carbachol caused by antigen challenge and almost abolished the concentration-response curves to KCl, whereas it had little effect on the concentration-response curves to carbachol. Under Ca(2+)-free conditions and in the presence of 10(-4) mol/L acetylcholine, neither 1,8-cineole (6.5 x 10(-3) mol/L) nor verapamil (1 x 10(-5) mol/L) affected Ca(2+)-induced contractions, but they almost abolished Ba(2+)-induced contractions. 4. In conclusion, the findings of the present study show that 1,8-cineole is a tracheal myorelaxant that acts preferentially on contractile responses elicited electromechanically.
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