ABSTRACT
UNLABELLED: We studied relaxation of airway smooth muscle by sevoflurane, desflurane, and halothane in isolated guinea pig bronchi. Ring preparations were mounted in tissue baths filled with physiological salt solution and continuously aerated with 5% CO(2) in oxygen. Electrical field stimulation induced contractions sensitive to tetrodotoxin, indicating nerve-mediated responses. These consisted of an atropine-sensitive cholinergic phase and a nonadrenergic noncholinergic (NANC) phase sensitive to SR48968, a neurokinin-2 receptor antagonist. Anesthetics were added to the gas aerating the tissue baths. Sevoflurane and desflurane at 1.0 minimum alveolar anesthetic concentration and halothane at 1.0-2.0 minimum alveolar anesthetic concentrations inhibited both cholinergic and NANC contractions to electrical field stimulation. None of the anesthetics affected responses to exogenously applied neurokinin A, a likely mediator of NANC contractions, suggesting prejunctional inhibition of NANC neurotransmission. The anesthetics did not affect the initiation of contractile responses to leukotriene C(4) (LTC(4)), a mediator of asthmatic bronchoconstriction. However, sevoflurane and desflurane both relaxed bronchi in a steady-state contraction achieved by LTC(4). Surprisingly, halothane did not relax LTC(4) contractions. Concerning LTC(4)-elicited bronchoconstriction, sevoflurane and desflurane were more potent airway smooth muscle relaxants in vitro. IMPLICATIONS: Halothane, sevoflurane, and desflurane attenuated airway smooth muscle tone via inhibition of cholinergic and nonadrenergic noncholinergic neurotransmission. Sevoflurane and desflurane reduced leukotriene C(4)-induced bronchoconstriction, whereas halothane did not. This indicates a beneficial role for sevoflurane and desflurane in asthmatics.
Subject(s)
Anesthetics, Inhalation/pharmacology , Bronchi/drug effects , Leukotriene C4/pharmacology , Muscle, Smooth/drug effects , Neurokinin A/pharmacology , Parasympathetic Nervous System/drug effects , Animals , Bronchi/innervation , Bronchi/physiology , Dose-Response Relationship, Drug , Electric Stimulation , Guinea Pigs , In Vitro Techniques , Muscle Contraction/drug effects , Muscle, Smooth/physiologyABSTRACT
We have studied relaxation of airway smooth muscle by sevoflurane, desflurane and halothane in the isolated guinea-pig trachea. Ring preparations were mounted in tissue baths filled with physiological salt solution (PSS), aerated continuously with 5% carbon dioxide in oxygen. Electrical field stimulation (EFS) elicited cholinergic contractions that were abolished by tetrodotoxin, indicating nerve-mediated responses. Anaesthetics were added to the gas aerating the tissue baths. Halothane, sevoflurane and desflurane at 0.5-1.0 MAC markedly attenuated cholinergic contractions to EFS. Initiation of contractile responses to acetylcholine (ACh) were not affected by volatile anaesthetics, suggesting prejunctional inhibition (i.e. inhibition of acetylcholine release). When added to a maintained submaximal contraction to ACh, volatile anaesthetics induced relaxation, indicating postjunctional inhibition. We conclude that sevoflurane, desflurane and halothane inhibited postganglionic cholinergic neuroeffector transmission in the trachea. The effect was probably exerted via pre- and postjunctional mechanisms (i.e. inhibition of acetylcholine release and direct muscle actions). Sevoflurane and desflurane were more potent than halothane both pre- and postjunctionally.
