The effect of ouabain on tension in isolated respiratory tract smooth muscle of humans and other species.
1. The 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-1; up to 1.8 g) developed within 25 min. 3. Ouabain (10(-7)-10(-5) 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(-5) 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.
Department of Medicine, West Virginia University, Morgantown 26506.
E W
EW
Chideckel
J L
JL
Frost
P
P
Mike
J S
JS
Fedan
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004285:Dogs; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010042:Ouabain / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D012137:Respiratory System / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D010042:Ouabain; D012964:Sodium; D011188:Potassium; D002118:Calcium