The role of nitric oxide in diaphragmatic dysfunction in endotoxemic rats

Muscle Nerve. 2001 Jan;24(1):30-6. doi: 10.1002/1097-4598(200101)24:1<30::aid-mus3>3.0.co;2-w.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Benzamides / pharmacology
  • Diaphragm / metabolism*
  • Diaphragm / physiopathology*
  • Endotoxemia / metabolism*
  • Endotoxemia / physiopathology*
  • Enzyme Inhibitors / pharmacology
  • Free Radicals / metabolism
  • Guanidines / pharmacology
  • In Vitro Techniques
  • Lipopolysaccharides
  • Male
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Muscle Fatigue / drug effects
  • Muscle Fatigue / physiology
  • Nitric Oxide / metabolism*
  • Nitric Oxide / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time

Substances

  • Benzamides
  • Enzyme Inhibitors
  • Free Radicals
  • Guanidines
  • Lipopolysaccharides
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Nitric Oxide
  • 3-aminobenzamide
  • Adenosine Triphosphate
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Poly(ADP-ribose) Polymerases
  • pimagedine