Spontaneous activity in the trachea of dogs treated with indomethacin: an experimental model for aspirin-related asthma

Abstract

1 Electrical and mechanical properties of smooth muscle cells or of neuro-effector transmission in the smooth muscle layer of the dog trachea, were studied after treatment with indomethacin, by means of the double sucrose gap, microelectrode or tension recording methods. 2 After several subcutaneous injections of indomethacin (1.0 mg/kg daily), 6 out of 12 dogs were coughing and wheezing. 3 Smooth muscle tissues dissected from the trachea of the coughing dog showed spontaneous electrical and mechanical activities at the frequency of 8-15 per min. These spontaneous electrical and mechanical activities were completely suppressed by treatment with atropine (10(-6) M), isoprenaline (5 X 10(-7) M) or prostaglandin E2 (10(-9) M) but not by tetrodotoxin (1.5 X 10(-6) M). 4 Direct muscle stimulation induced oscillatory potential changes followed by tension development in the trachea of the indomethacin-treated dog. 5 In the indomethacin-treated dog, mean membrane potential of the tracheal smooth muscle cells was -52.4 mV, and in the control trachea, the potential was -59.0 mV. 6 In the trachea from control dogs, the amplitude of test e.j.ps after conditioning e.j.ps was always smaller than the conditioning e.j.p., at any time interval between the two stimuli. In the trachea from indomethacin-treated dogs, facilitation phenomena were observed. 7 In the trachea from the indomethacin-treated dog, prostaglandin E1 (PGE1) or PGE2 (10(-10)-10(-9) M) markedly suppressed the amplitude of the e.j.p. but did not affect the facilitation phenomenon. 8 These results indicate that endogenous prostaglandins play important physiological roles in the feed-back inhibitory mechanisms for acetylcholine release from the nerve terminals during the resting and active states. 9 The results are also discussed in relation to the genesis of aspirin-induced asthma in man.