Interaction between volatile anesthetics and hypoxia in porcine tracheal smooth muscle.
We investigated the direct interaction between the volatile anesthetics, isoflurane and sevoflurane, and hypoxia in porcine tracheal smooth muscle in vitro by simultaneously measuring muscle tension and intracellular concentration of free Ca(2+) ([Ca2+]i). Muscle tension was measured by using an isometric transducer, and [Ca2+]i was measured by using fura-2, an indicator of Ca2+. Under the condition of bubbling with 95% O2/5% CO2, [Ca2+]i was increased by 1 microM carbachol with a concomitant contraction. Volatile anesthetics significantly inhibited both carbachol-induced muscle contraction and increase in [Ca2+]i. Hypoxia bubbled with 95% N(2)/5% CO2 inhibited the muscle contraction by 30% with an increase in [Ca2+]i by 20%. Exposure to hypoxia substantially enhanced the inhibitory effects of these anesthetics on carbachol-induced muscle contraction, whereas the decreases in [Ca2+]i were significantly prevented by hypoxia. Under Ca2+-free conditions, hypoxia significantly decreased the muscle contraction by 20%; however, it still increased [Ca2+]i by 15%. Exposure to the anesthetics significantly enhanced the inhibitory effect of hypoxia on the muscle contraction; however, it appeared to have little effect on [Ca2+]i. Hypoxia inhibits airway smooth muscle contraction independently of intracellular Ca2+, and it substantially potentiates the inhibitory effects of volatile anesthetics on airway smooth muscle contraction.


CONCLUSIONS
Hypoxia inhibits agonist-induced tracheal smooth muscle contraction with an increase in free Ca2+ [Ca2+]i, which comes from intracellular Ca2+ stores. Hypoxia also potentiates the inhibitory effect of volatile anesthetics on airway smooth muscle contraction. Conversely, there is a possibility that the treatment of asthmatic patients with oxygen partially attenuates the inhibitory effect of volatile anesthetics on airway smooth muscle contractility.
Chen
X
X
Department of Anesthesiology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Yamakage
M
M
Tsujiguchi
N
N
Kamada
Y
Y
Namiki
A
A
D000704:Analysis of Variance; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000032:analysis; D020013:Calcium Signaling / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002614:Chelating Agents; D018679:Cholinergic Agonists / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000503:physiopathology*; D007530:Isoflurane / Q000494:pharmacology*; D007537:Isometric Contraction / Q000187:drug effects; D008738:Methyl Ethers / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology; D009584:Nitrogen / Q000008:administration & dosage; D010100:Oxygen / Q000008:administration & dosage; D000077149:Sevoflurane; D013050:Spectrometry, Fluorescence; D013552:Swine; D014132:Trachea / Q000187:drug effects* / Q000503:physiopathology; D014159:Transducers
D018685:Anesthetics, Inhalation; D002614:Chelating Agents; D018679:Cholinergic Agonists; D005456:Fluorescent Dyes; D008738:Methyl Ethers; D018721:Muscarinic Agonists; D000077149:Sevoflurane; D002217:Carbachol; D007530:Isoflurane; D009584:Nitrogen; D010100:Oxygen; D002118:Calcium; D016257:Fura-2