[Role of nitric oxide in diaphragmatic dysfunction genesis during sepsis in rats].
Nitric oxide (NO) is a vasodilator agent that is cytotoxic and negatively inotropic in the heart. More recently, it has been shown that during sepsis there is a high amount of NO production by a NO synthase (NOS) that is inducible by cytokines. The aim of this study was to investigate the role of NO in the genesis of diaphragmatic dysfunction during sepsis. Rats were inoculated i.p. injection with 10 mg/kg of Escherichia coil endotoxin (E animals) or saline (C animals). Six hours after endotoxin or saline inoculation, diaphragmatic force and muscularc GMP (Cyclic guanosine monophosphate) were assessed by in vitro force frequency curves and ELISA method, respectively. As compared to C animals, E animals showed a significant decrease in diaphragmatic force for all the frequencies of stimulation (p < 0.01). This reduction was associated with a significant increase in muscular cGMP. Inhibition of NO synthesis in E animals with either dexamethasone (4 mg/kg IV, 45 min before endotoxin or saline) or NG-monomethyl-L-arginine (L-NMMA, 8 mg/kg IV, 90 min after endotoxin or saline) prevented the effects of endotoxin. However, no modification was seen with NG-monomethyl-D-arginine (D-NMMA), a molecule which does not inhibit NO synthesis. Administration of dexamethasone or L-NMMA in C animals did not induce any significant change in diaphragmatic force, and cGMP ratio. We conclude that NO has a contributive role in diaphragmatic dysfunction during Escherichia coli induced sepsis in rats.
Samb
A
A
Laboratoire de Physiologie, Faculté de Médecine et Pharmacie, Dakar, Sénégal.
Boczkowski
J
J
Danialou
G
G
Lanone
S
S
Cisse
F
F
Aubier
M
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001706:Biopsy; D006152:Cyclic GMP / Q000032:analysis / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000150:complications* / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D004927:Escherichia coli Infections / Q000150:complications* / Q000276:immunology; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics; D012133:Respiratory Paralysis / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology / Q000503:physiopathology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP