Nitric oxide and ATP-sensitive potassium channels mediate lipopolysaccharide-induced depression of central respiratory-like activity in brain slices.
Infection may result in early abnormalities in respiratory movement, and the mechanism may involve central and peripheral factors. Peripheral mechanisms include lung injury and alterations in electrolytes and body temperature, but the central mechanisms remain unclear. In the present study, brainstem slices harvested from rats were stimulated with lipopolysaccharide at different doses. Central respiratory activities as demonstrated by electrophysiological activity of the hypoglossal rootlets were examined and the mechanisms were investigated by inhibiting nitric oxide synthase and ATP-sensitive potassium channels. As a result, 0.5 μg/ml lipopolysaccharide mainly caused inhibitory responses in both the frequency and the output intensity, while 5 μg/ml lipopolysaccharide caused an early frequency increase followed by delayed decreases in both the frequency and the output intensity. At both concentrations the inhibitory responses were fully reversed by inhibition of nitric oxide synthase with Nω-nitro-L-arginine methyl ester hydrochloride (20 μM), and by inhibition of ATP- sensitive potassium channels with glybenclamide (100 μM). These results show that direct lipopolysaccharide challenge altered central respiratory activity in dose- and time- related manners. Nitric oxide synthase and ATP-sensitive potassium channels may be involved in the respiratory changes.
Department of Anesthesiology and Intensive Care Medicine, Changhai Hospital, the Second Military Medical University, Shanghai, China.
An-Dong
AD
Lu
Jia-Feng
JF
Wang
Yong-Hua
YH
Chen
Li-Li
LL
Hou
Xu-Jiao
XJ
Zhou
Jin-Jun
JJ
Bian
Ji-Jiang
JJ
Wang
Ke-ming
KM
Zhu
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D054086:KATP Channels / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D054086:KATP Channels; D008070:Lipopolysaccharides; D026902:Potassium Channel Blockers; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester