Involvement of nitric oxide system in experimental muscle crush injury

J Clin Invest. 1998 Mar 15;101(6):1325-33. doi: 10.1172/JCI810.

Abstract

Muscle crush injury is often complicated by hemodynamic shock, electrolyte disorders, and myoglobinuric renal failure. In this study, we examined the involvement of the nitric oxide (NO) system in the development of muscle damage in an experimental model of crush injury induced by exertion of standardized mechanical pressure on tibialis muscle of rat. The intact limb served as a control. Four days after injury, the crushed muscle was characterized by extreme capillary vasodilatation as demonstrated by histological morphometric analysis. These changes were accompanied by muscle hyperperfusion as evaluated by measurements of femoral blood flow (ultrasonic flowmetry) and capillary blood flow (laser-doppler flowmetry). Treatment with Nomega-nitro-L-arginine methyl ester, a NO synthase (NOS) inhibitor, largely decreased the hyperperfusion. Furthermore, the expression of the different NOS isoforms, assessed by reverse transcription-PCR and immunoreactive levels, determined by Western blot, revealed a remarkable induction of the inducible NOS in the crushed limb. Similarly, endothelial NOS mRNA increased gradually after the induction of muscle damage. In contrast, the major muscular NOS, i.e., neuronal isoform remained unchanged. In line with the alterations in the mRNA levels, Western blot analysis revealed parallel changes in the immunoreactive levels of the various NOS. These findings indicate that muscle crush is associated with activation of the NO system mainly due to enhancement of iNOS. This may contribute to NO-dependent extreme vasodilatation in the injured muscle and aggravate the hypovolemic shock after crush injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Flow Velocity
  • Blotting, Western
  • Capillaries / physiopathology
  • Dilatation, Pathologic / physiopathology
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / metabolism
  • Enzyme Inhibitors / pharmacology
  • Femoral Artery / physiopathology
  • Hindlimb / injuries
  • Hindlimb / metabolism
  • Isoenzymes / genetics
  • Isoenzymes / immunology
  • Isoenzymes / metabolism
  • Muscle, Skeletal / blood supply
  • Muscle, Skeletal / injuries*
  • Muscle, Skeletal / metabolism*
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Enzyme Inhibitors
  • Isoenzymes
  • RNA, Messenger
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos1 protein, rat
  • Nos2 protein, rat
  • Nos3 protein, rat
  • NG-Nitroarginine Methyl Ester