Effects of neuromuscular blocking agents on central respiratory chemosensitivity in newborn rats.
Neuromuscular blocking agents suppress central respiratory activity through their inhibitory effects on preinspiratory neurons and the synaptic drive from preinspiratory neurons to inspiratory neurons. Central CO2-chemosensitive areas, which partly consist of CO2-excited neurons, in the rostral ventrolateral medulla are thought to provide tonic drive to the central respiratory network and involve cholinergic mechanisms, which led us to hypothesize that neuromuscular blocking agents can inhibit CO2-excited neurons and attenuate respiratory CO2 responsiveness. To test this hypothesis, we used isolated brainstem-spinal cord preparations from newborn rats. The increase of C4 burst frequency induced by a hypercapnic superfusate, i.e. respiratory CO2 responsiveness, was suppressed by the application of neuromuscular blocking agents, either d-tubocurarine (10, 100 microM) or vecuronium (100 microM). These agents (40 microM) also induced hyperpolarization and decreases in firing frequency of CO2-excited neurons in the rostral ventrolateral medulla. Our results demonstrate that neuromuscular blocking agents inhibit CO2-excited tonic firing neurons and attenuate respiratory CO2 responsiveness.
Sakuraba
Shigeki
S
Department of Anesthesiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Shigeki.Sakuraba@kirurgi.ki.se
Kuwana
Shun-Ichi
S
Eriksson
Lars I
LI
Okada
Yasumasa
Y
Ochiai
Ryoichi
R
Kashiwagi
Masanori
M
Hatori
Eiki
E
Lindahl
Sten G E
SG
Takeda
Junzo
J
D000818:Animals; D000831:Animals, Newborn; D002245:Carbon Dioxide / Q000502:physiology; D002628:Chemoreceptor Cells / Q000187:drug effects*; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects*; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects; D012125:Respiratory Center / Q000187:drug effects* / Q000502:physiology; D014403:Tubocurarine / Q000494:pharmacology; D014673:Vecuronium Bromide / Q000494:pharmacology
D003473:Neuromuscular Nondepolarizing Agents; D002245:Carbon Dioxide; D014673:Vecuronium Bromide; D014403:Tubocurarine