Differential effects of halothane and thiopental on surfactant protein C messenger RNA in vivo and in vitro in rats.
BACKGROUND
Pulmonary surfactant is a complex mixture of proteins and phospholipids synthetized by alveolar type II cells. Volatile anesthetics have been shown to reduce surfactant phospholipid biosynthesis by rat alveolar type II cells. Surfactant-associated protein C (SP-C) is critical for the alveolar surfactant functions. Our goal was to evaluate the effects of halothane and thiopental on SP-C messenger RNA (mRNA) expression in vitro in rat alveolar type II cells and in vivo in mechanically ventilated rats.


METHODS
In vitro, freshly isolated alveolar type II cells were exposed to halothane during 4 h (1, 2, 4%) and 8 h (1%), and to thiopental during 4 h (10, 100 micrometer) and 8 h (100 micrometer). In vivo, rats were anesthetized with intraperitoneal thiopental or inhaled 1% halothane and mechanically ventilated for 4 or 8 h. SP-C mRNA expression was evaluated by ribonuclease protection assay.


RESULTS
In vitro, 4-h exposure of alveolar type II cells to thiopental 10 and 100 micrometer increased their SP-C mRNA content to 145 and 197%, respectively, of the control values. In alveolar type II cells exposed for 4 h to halothane 1, 2, and 4%, the SP-C mRNA content increased dose-dependently to 160, 235, and 275%, respectively, of the control values. In vivo, in mechanically ventilated rats, 4 h of halothane anesthesia decreased the lung SP-C mRNA content to 53% of the value obtained in control (nonanesthetized, nonventilated) animals; thiopental anesthesia increased to 150% the lung SP-C mRNA content.


CONCLUSIONS
These findings indicate that halothane and thiopental used at clinically relevant concentrations modulate the pulmonary SP-C mRNA content in rats. In vivo, the additive role of mechanical ventilation is suggested.
Paugam-Burtz
C
C
Unité Inserm 408, Faculté X. Bichat, Paris, France.
Molliex
S
S
Lardeux
B
B
Rolland
C
C
Aubier
M
M
Desmonts
J M
JM
Crestani
B
B
D000199:Actins / Q000235:genetics; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D006221:Halothane / Q000494:pharmacology*; D008297:Male; D011510:Proteolipids / Q000235:genetics*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial; D013874:Thiopental / Q000494:pharmacology*
D000199:Actins; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D011510:Proteolipids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D013874:Thiopental; D006221:Halothane