The Effects Of Endotoxin On ATP-sensitive Potassium Channels In Medullary Respiratory Center Neurons In Neonatal Rats And Its Mechanism

In sepsis lung often is the most involved damaged organ. Faster spontaneous breathing frequency is a typical example of acute lung injury in sepsis, acute hypoxia is generally considered the body caused by lung and compensatory response.However little is known regarding whether and how the neuroinflammatory changes potentially occurring in respiratory centers contribute to the alterations in respiratory movement. In this study respiratory activity was recorded from hypoglossal rootlets of brainstem slices of newborn rats; the effects of lipopolysaccharide on central respiratory activity were examined and the mechanisms were investigated. The results show that at 0.5μg/ml lipopolysaccharide mainly caused inhibitory responses in both the frequency and output intensity; at 5μg/ml lipopolysaccharide caused an early frequency increase followed by delayed decreases in both the frequency and 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 (20μM), and by inhibition of ATP-sensitive potassium channels with glybenclamide (100μM). These results prove that direct lipopolysaccharide challenge altered central respiratory activity; the inhibitory responses involved of nitric oxide and ATP-sensitive potassium channels. These results suggest that in sepsis the neuroinflammatory changes in respiratory centers contribute to the alterations of respiratory movement, and both nitric oxide synthase and ATP-sensitive potassium channels are prospective targets for treatment of the respiratory dysfunctions.