Effect of cooling on responses of isolated human airways to pharmacologic and electrical stimulation.
We studied the effect of cooling on the responses of isolated human airways to the beta-agonist isoproterenol, the alpha/beta-agonist norepinephrine in the presence of the beta-blocker timolol, methacholine, leukotriene C4 (LTC4), and histamine. In addition, the effect of cooling on baseline airway tone and responses to electric field stimulation (EFS) was studied. At 27 degrees C the sensitivity (-logEC50) and maximal response to isoproterenol were unchanged. No measurable response was found to alpha-adrenergic stimulation with norepinephrine + timolol either before or during cooling. At 27 degrees C and 21 degrees C the sensitivity and maximal contraction to methacholine and LTC4 as well as the contraction to a single dose of histamine were reduced. Cooling diminished baseline airway tone. EFS produced a rapid cholinergic contraction followed by a deflection below baseline and a sustained noncholinergic contractile response, which was substantially reduced by the LTC4/D4 receptor antagonist FPL 55712 (11.5 microM) at all three temperatures. Cooling decreased the cholinergic response to EFS and increased the sensitivity to EFS-induced relaxation. In contrast, the sustained noncholinergic contractile response to EFS was not changed, suggesting that cooling facilitates the synthesis of LTC4/D4 that follows EFS and/or inhibits its inactivation. We conclude that in nonasthmatic, isolated human airways slow cooling of the airway wall down to 21 degrees C does not cause bronchoconstriction and does not increase the responsiveness to contractile or relaxing agonists. However, cooling increases the sensitivity to EFS-induced relaxation and might facilitate the accumulation of leukotriene C4/D4 in the airway wall.(ABSTRACT TRUNCATED AT 250 WORDS)
Jongejan
R C
RC
Department of Pediatric Pulmonary Medicine, Erasmus University, Rotterdam, The Netherlands.
De Jongste
J C
JC
Raatgeep
R C
RC
Bonta
I L
IL
Kerrebijn
K F
KF
D000328:Adult; D000368:Aged; D003080:Cold Temperature; D004558:Electric Stimulation; D004848:Epithelium / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D013189:SRS-A / Q000494:pharmacology; D013268:Stimulation, Chemical; D013566:Sympathomimetics / Q000494:pharmacology
D013189:SRS-A; D013566:Sympathomimetics; D016210:Methacholine Chloride