Dysfunction of the mitochondrial respiratory chain in the rostral ventrolateral medulla during experimental endotoxemia in the rat.
We investigated the functional changes in the mitochondrial respiratory chain at the rostral ventrolateral medulla (RVLM), the medullary origin of sympathetic vasomotor tone, in an experimental model of endotoxemia that mimics systemic inflammatory response syndrome. In Sprague-Dawley rats maintained under propofol anesthesia, intravenous administration of Escherichia coli lipopolysaccharide (LPS; 30 mg/kg) induced a reduction (Phase I), followed by an augmentation (Phase II) and a secondary decrease (Phase III) in the power density of vasomotor components (0-0.8 Hz) in systemic arterial pressure signals. LPS also elicited progressive hypotension, and death ensued within 4 h. Enzyme assay revealed significant depression of the activity of nicotinamide adenine dinucleotide cytochrome c reductase (Complexes I + III) and cytochrome c oxidase (Complex IV) in the RVLM during all three phases of endotoxemia. On the other hand, the activity of succinate cytochrome c reductase (Complexes II + III) remained unaltered. We conclude that selective dysfunction of respiratory enzyme Complexes I and IV in the mitochondrial respiratory chain at the RVLM, whose neuronal activity is intimately related to the death process, is closely associated with fatal endotoxemia in the rat.
Chuang
Yao-Chung
YC
Department of Biological Science, National Sun Yat-sen University, Kaohsiung, Taiwan, ROC.
Tsai
Jin-Lian
JL
Chang
Alice Y W
AY
Chan
Julie Y H
JY
Liou
Chai-Wei
CW
Chan
Samuel H H
SH
D000818:Animals; D004195:Disease Models, Animal; D004579:Electron Transport; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D019446:Endotoxemia / Q000378:metabolism / Q000503:physiopathology*; D006339:Heart Rate; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism / Q000503:physiopathology*; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000503:physiopathology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000401:mortality / Q000503:physiopathology
D009247:NADH, NADPH Oxidoreductases; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III