Inhibitory effects of four inhaled anesthetics on canine tracheal smooth muscle contraction and intracellular Ca2+ concentration.
To clarify the mechanisms by which inhaled anesthetics directly inhibit tracheal smooth muscle contraction, we investigated the effects of these anesthetics on muscle tension and intracellular Ca2+ concentration ([Ca2+]i). Tension was measured using an isometric transducer, and [Ca2+]i was measured using Fura-2, an indicator of [Ca2+]i. Addition of 1 microM carbachol increased muscle tension and [Ca2+]i. All inhaled anesthetics significantly decreased both muscle tension and [Ca2+]i in the following order of inhibitory potency: halothane >> isoflurane > enflurane >> sevoflurane. In the presence of 10 microM verapamil, carbachol moderately increased muscle tension, but induced a transient increase of [Ca2+]i followed by a substantial reduction. Inhaled anesthetics in the presence of both carbachol and verapamil significantly decreased muscle tension without decreasing [Ca2+]i. Potency for suppression of tension under these conditions, which appeared to be independent of [Ca2+]i, was in the order: halothane >> enflurane > or = isoflurane >> sevoflurane. The best correlation we found with a measured reduction of muscle tension independent of [Ca2+]i was with oil/gas partition coefficients (r = -0.88, P < 0.001). In conclusion, inhaled anesthetics inhibit tracheal smooth muscle contraction by at least two mechanisms: 1) reduction of [Ca2+]i and 2) suppression of contractility, independent of [Ca2+]i. The close correlation between the muscle inhibition independent of [Ca2+]i and the oil/gas partition coefficients suggests that one of the major sites of action of inhaled anesthetics is membrane phospholipids.
Yamakage
M
M
Department of Anesthesiology, Sapporo Medical College, Japan.
Kohro
S
S
Kawamata
T
T
Namiki
A
A
D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D004737:Enflurane / Q000494:pharmacology*; D004987:Ethers / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology*; D007530:Isoflurane / Q000494:pharmacology*; D008738:Methyl Ethers; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D000077149:Sevoflurane; D014132:Trachea / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D000777:Anesthetics; D004987:Ethers; D008738:Methyl Ethers; D000077149:Sevoflurane; D002217:Carbachol; D004737:Enflurane; D014700:Verapamil; D007530:Isoflurane; D002118:Calcium; D006221:Halothane