title: The role of nitric oxide in diaphragmatic dysfunction in endotoxemic rats.
abstract: In this study we examined the role of nitric oxide (NO) from inducible nitric oxide synthase (iNOS) and adenosine triphosphate (ATP) depletion, using aminoguanidine and 3-aminobenzamide, on diaphragm contractility in a rat model of sepsis. Intraperitoneal lipopolysaccharide (LPS) injection was used to induce septicemia in rats. The LPS treatment caused a decrease in maximal 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 more fatigable than controls. The decrease in force in LPS-treated animals was not due to an induction of pathological levels of i NOS. Increased fatigability did not appear to be due to a depletion of ATP through poly-adenosine-diphosphate-ribose polymerase (PARP) activation. This study does not support the hypothesis that the decrease in diaphragm muscle force as a result of sepsis is due to an induction of pathological levels of nitric oxide or ATP depletion.
authors.affiliation: School of Physiology and Pharmacology, University of New South Wales, Sydney, 2052, Australia.
authors.forename: J L
authors.initials: JL
authors.lastname: Anderson
authors.forename: G
authors.initials: G
authors.lastname: Williams
authors.forename: S I
authors.initials: SI
authors.lastname: Head
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D003964:Diaphragm / Q000378:metabolism* / Q000503:physiopathology*; D019446:Endotoxemia / Q000378:metabolism* / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018763:Muscle Fatigue / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time
chemical_list: D001549:Benzamides; D004791:Enzyme Inhibitors; D005609:Free Radicals; D006146:Guanidines; D008070:Lipopolysaccharides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009569:Nitric Oxide; C025160:3-aminobenzamide; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D011065:Poly(ADP-ribose) Polymerases; C004479:pimagedine