Halothane- and enflurane-induced inhibition of phasic responses to carbachol in isolated guinea pig trachea.
Volatile anesthetics produce bronchodilatation by a combination of effects on the autonomic nervous system as well as direct effects on the airway smooth muscle. We sought to further explain the direct effects on airway smooth muscle by studying the effect of volatile anesthetics on the phasic and tonic components of the contractile response. The effects of 1.2%, 2.3%, and 4.3% halothane and 1.6%, 3.2%, 4.9%, and 8.7% enflurane on the phasic and tonic components of the contractile response to 10 microM carbachol and 40 mM KCl in isolated guinea pig trachea were determined using steady-state and kinetic analyses. No direct effect of either anesthetic on resting tension was observed. The peak tensions of the phasic responses to 10 microM carbachol were significantly inhibited by all concentrations of halothane and enflurane. The inhibition by enflurane was concentration-dependent and eliminated the phasic response at 8.7%. The peak tensions of the tonic responses to 10 microM carbachol were unaffected. The peak tensions of the responses to 40 mM KCl were unaffected by halothane but were significantly inhibited by 4.9% enflurane. The decay rate of the phasic response was unaffected by the anesthetics. The onset rate of the tonic response was significantly inhibited only by 8.7% enflurane, whereas halothane was without effect. The EC50 concentration for carbachol, as determined by cumulative concentration response curves, was increased by both 8.7% enflurane and 4.3% halothane. The results support the hypothesis that halothane and enflurane inhibit that portion of the contractile response to carbachol dependent on the release of intracellular Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)
Tagliente
T M
TM
Department of Anesthesiology, Mount Sinai School of Medicine, City University of New York, New York.
Evans
P J
PJ
Ben-Harari
R R
RR
D000818:Animals; D002217:Carbachol / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D004737:Enflurane / Q000494:pharmacology*; D006168:Guinea Pigs; D006221:Halothane / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D014132:Trachea / Q000187:drug effects
D002217:Carbachol; D004737:Enflurane; D006221:Halothane