The role of nitric oxide in diaphragmatic dysfunction in endotoxemic rats

In this study we examined the role of nitric oxide (NO) from inducible nitr ic oxide synthase (iNOS) and adenosine triphosphate (ATP) depletion, using aminoguanidine and 3-aminobenzamide, on diaphragm contractility in a rat mo del of sepsis, Intraperitoneal lipopolysaccharide (LPS) injection was used to induce septicemia in rats. The LPS treatment caused a decrease in maxima l absolute force produced by the diaphragm muscle stimulated at 100 Hz, and the force-frequency curves were right-shifted with a decrease in force at 2, 5 and 15 Hz. LPS administration also made the diaphragm muscle strips mo re fatigable than controls. The decrease in force in LPS-treated animals wa s not due to an induction of pathological levels of iNOS. Increased fatigab ility did not appear to be due to a depletion of ATP through poly-adenosine -diphosphate-ribose polymerase (PARP) activation. This study does not suppo rt the hypothesis that the decrease in diaphragm muscle force as a result o f sepsis is due to an induction of pathological levels of nitric oxide or A TP depletion. (C) 2001 John Wiley & Sons, Inc.