The effect of ouabain on tension in isolated respiratory tract smooth muscle of humans and other species

Abstract

1The Na', K+-pump has been implicated in animal models of airway hyperreactivity. We examined the effects of inhibiting the Na', K+-pump and Na+, Ca2+-exchange on isometric tone of isolated trachealis from humans and other species. 2 In preparations from 5 out of 9 humans, strong spontaneous contractions (36-48 h-'; up to 1.8 g) developed within 25 min. 3 Ouabain (10-7-10-'M) caused an immediate and sustained contraction. This response was not blocked by atropine, diphenhydramine, or cimetidine. 4 Contractions were also elicited when the normal physiological solution was changed to a K+-free solution, a procedure which inhibits the Na+, K+-pump, and in reduced (15 mM) Na+ solution, which inhibits Na+, Ca2+ exchange. 5 In preparations of dog and guinea-pig isolated trachea, ouabain (10-M) caused a multiphasic response; in the rabbit, ouabain was without effect. K+-free solution was without effect in the dog preparations and produced relaxation of the guinea-pig trachea. Guinea-pig tracheae responded to a low Na+ solution with a strong contraction. 6 Our findings indicate that: (a) human airway smooth muscle may be a spontaneously contracting muscle, at least in vitro, (b) a prolonged contraction to ouabain is unique for the human airway smooth muscle among the animals tested, as is the contraction in a K+-free medium, and (c) the contractile response does not involve acetylcholine or histamine release, but may involve a Na+, Ca2+-exchange mechanism. These results suggest that the level of Na+, K+-pump activity could play a role in determining the degree of bronchomotor tone in humans.

Influence of Ouabain on the Tracheal Musculature of the Dog

“…Al though it is known that an active electrogenic pump is present in the smooth muscle of the guinea pig and bovine airway (19), it remains to be determined whether the Na+ electro genic pump is present in the canine trachea. It has been reported that a K+-free solution has no effect on the isolated canine trachea (5). In the present study, the tracheal con striction that remained after bilateral vagotomy was almost completely abolished by atropine.…”

“…Tracheal constriction occurred at a total dose of 45.0±5. 5 ag/kg (n=5) of ouabain. When the total dose of ouabain reached 54.4±6.1 ug/kg (n=5), a decrease in heart rate occurred.…”

“…Inhibition of Na+,K+-ATPase activity also induces contractions in various types of isolated smooth muscles (1-3), including airway smooth muscle (4,5). In situ, ther apeutic amounts of cardiac glycosides are known to enhance efferent vagal activity to the heart by means of the following me chanisms:…”

The effects of alterations in electrogenic Na+/K+‐pumping in guinea‐pig isolated trachealis: their modulation by the epithelium

“…This effect, not observed by , was seen by Chideckel et al (1987). It is possible that, in our experiments, hyperpolarization in K+-free MKH has a greater initial effect on membrane potential than depolarization resulting from inhibition of electrogenic pump current (Fleming, 1980).…”

The spontaneous electrical and mechanical activity of human bronchial smooth muscle: its modulation by drugs

“…;et al, 1982). A more recent report showed that spontaneous contraction developed in 4 out of 5 human tissues, within 25 min of the start of tissue incubation in an organ bath (Chideckel et al, 1987). However, in these two studies, the human tracheal tissue originated mainly from cadavers.…”