The inhibition of sodium influx attenuates airway response to a specific antigen challenge.
1. We have previously observed that manipulation of Na+ availability during passive in vitro sensitization altered electrophysiological and contractile changes of airway smooth muscle cells. The purpose of this study was to establish whether interference with Na+ influx during sensitization also influences the response of airway smooth muscle, both in vivo and in vitro, to a specific antigen challenge. 2. Isolated segments of trachea which had been sensitized to ovalbumin in the presence of the Na+ channel-blocking agent amiloride (10(-5) M) showed no electrical or contractile response to ovalbumin in spite of their ability to respond to histamine (10(-5) M). 3. Airway smooth muscle preparations sensitized to ovalbumin in a Na+-deficient medium failed to show any contractile response after exposure to ovalbumin and only a small depolarization of airway smooth muscle cells was detected. 4. Guinea-pigs were passively sensitized in vivo either in the absence of, or following pretreatment with, amiloride (1 mg kg-1 s.c.). These animals were then exposed to an ovalbumin inhalation challenge and both lung resistance (RL) and dynamic lung compliance (Cdyn) were measured. 5. After an inhalation challenge of sensitized animals, we observed a significant increase in lung resistance (RL) achieving a maximum of 489% of the baseline values and a decrease in dynamic lung compliance (Cdyn). Twenty min after ovalbumin challenge Cdyn was equivalent to 20% of baseline values. 6. In animals pretreated with amiloride during sensitization, the inhalation challenge caused only a small increase in RL achieving a maximum increase of 148% of baseline values, and a small decrease in Cdyn. Twenty min after ovalbumin challenge Cdy. was equivalent to 98% of baseline values. 7. We concluded that interference with Na' influx during both in vitro and in vivo sensitization attenuates the contractile and electrical responses of airway smooth muscle preparations or the changes in lung resistance and compliance observed after antigen challenge.
Souhrada
M
M
John B. Pierce Foundation Laboratory, New Haven, CT 06519.
Souhrada
M H
MH
Souhrada
J F
JF
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism; D007116:Immunization, Passive; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D012119:Respiration / Q000187:drug effects; D012129:Respiratory Function Tests; D012964:Sodium / Q000378:metabolism*; D014132:Trachea / Q000187:drug effects
D000584:Amiloride; D006632:Histamine; D012964:Sodium