Acta Vet. Brno 2018, 87: 99-107
Effects of nonselective and selective cyclooxygenase inhibitors on the contractions of isolated bronchial smooth muscle in the horse
We evaluated the effects of nonselective cyclooxygenase (COX)-1/COX-2 inhibitors (acetylsalicylic acid, indomethacin, ibuprofen, flunixin meglumine, phenylbutazone), preferential COX-2 inhibitors (diclofenac, meloxicam, carprofen), selective COX-1 inhibitor (SC-560), and selective COX-2 inhibitors (celecoxib, firocoxib, parecoxib) on the contractions of isolated bronchi induced by electrical field stimulation (EFS). Bronchial rings, obtained from lungs of slaughtered horses, were put in isolated organ baths, and the mechanical activity was measured by means of isotonic transducers. Electrical Field Stimulation was applied to the preparations, and the effects of drugs on the amplitude of evoked contractions were measured. Nonselective COX inhibitors did not modify EFS-induced contractions to a relevant degree, except indomethacin which caused a concentration-dependent decrease of the contraction amplitude. Conversely, preferential COX-2 inhibitors enhanced the contractions in a concentration-related fashion, whilst the selective COX-1 inhibitor reduced them. Among selective COX-2 inhibitors, parecoxib increased EFS-evoked contractions whereas celecoxib and firocoxib were ineffective. These results suggest that the inhibition of prostanoid synthesis does not modify the electrical field-stimulated contractions of isolated horse bronchi. Since EFS-induced contractions of horse bronchi were previously shown to be of full cholinergic nature, the increase caused by diclofenac, meloxicam, carprofen, and parecoxib could be due to an inhibition of acetylcholinesterase; in accordance, these drugs potentiated exogenous acetylcholine-induced but not carbachol-induced bronchial contraction. Indomethacin and SC-560 might instead decrease bronchial contractions by inhibiting calcium currents. Clinical use of meloxicam and carprofen in horses with bronchial hyper-responsiveness requires caution for a potential risk of causing adverse effects due to bronchoconstriction.
Funding
This study was supported by a grant from the University of Parma (FIL 2014).
