Cooling-induced contraction in ovine airways smooth muscle

The mechanism of cold-induced bronchoconstriction is poorly understood. Thi s prompted the present study whose aim was to determine the step-wise direc t effect of cooling on smooth muscle of isolated ovine airways and analyse the role of calcium in the mechanisms involved. Isolated tracheal strips an d bronchial segments were suspended in organ baths containing Krebs' soluti on for isometric tension recording. Tissue responses during stepwise coolin g from 37 to 5 degrees C were examined. Cooling induced a rapid and reprodu cible contraction proportional to cooling temperature in ovine tracheal and bronchial preparations which was epithelium-independent. On readjustment t o 37 degrees C the tone returned rapidly to basal level. Maximum contractio n was achieved at a temperature of 5 degrees C for trachea and 15 degrees C for bronchiole. Cooling-induced contractions (CIC) was resistant to tetrod otoxin (1; 10 mu M), and not affected by the muscarinic antagonist atropine (1 mu M) or the alpha-adrenergic antagonist phentolamine (1 mu M), or the histamine H-1-antagonist mepyramine (1 mu M) or indomethacin (1 mu M). Ca2 antagonists (nifedipine and verapamil) and Mn2+ raised tracheal but not br onchiolar tone and augmented CIC. Incubation in Ca2+-free, EGTA-containing Krebs' solution for 5 min had no effect on CIC, although it significantly r educed KCl-induced contraction by up to 75%. Cooling inhibited Ca2+ influx measured using Ca-45(2+) uptake. Caffeine (100 mu M) significantly inhibite d CIC. The results show that cooling-induced contractions do not appear to involve activation of nerve endings, all surface reception systems or Ca2influx. However, CIC is mainly dependent on release of intracellular Ca2+ ( C) 1999 The Italian Pharmacological Society.