Nitric oxide metabolism in muscle mitochondria in endotoxic and septic shock

ALVAREZ, SILVIA; BOVERIS, ALBERTO

Progress in Inflammation Research

Nova Science

Lugar: Massachussets; Año: 2006; p. 72 - 88

Endotoxemia and septic shock occur with an exacerbated inflammatory response that damages tissue mitochondria. Skeletal muscle appears as one of the main target organs in septic shock, showing an increased nitric oxide (NO) production and an early oxidative stress. Heart and diaphragm mitochondria produced, in normal conditions, 67 and 24% of maximal total cellular NO production, and endotoxemic rats showed 30-90% increased mtNOS activity. Heart and diaphragm mitochondrial O2·- and H2O2 production were 2-3 increased during endotoxemia and Mn-SOD activity showed a 2 fold increase in treated animals. One of the current hypothesis for the molecular mechanisms underlying the complex condition of septic shock is that the enhanced NO production by mtNOS and cytosolic iNOS leads to excessive peroxynitrite production and protein nitration in the mitochondrial matrix, causing mitochondrial dysfunction and contractile failure. The available data suggest that impairment of mitochondrial function based on the pathological alteration of NO metabolism and on the production of toxic oxidative and nitrosative species, constitutes the basis of the molecular mechanism of organ dysfunction in endotoxic and septic shock. The high NO production by mtNOS and mitochondrial dysfunction, which are characteristics of the septic shock syndrome, open new avenues for experimentation and for the analisis of clinical data.