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The mechanisms of peroxynitrite-induced relaxations in isolated rat anococcygeus muscle

Feyza Ademoğlu1, Bilgen Başgut, Nurettin Abacioğlu

  • 1Department of Pharmacology, Faculty of Pharmacy, Gazi University, Ankara, Turkey. feyzade@yahoo.com

Pharmacology
|August 10, 2002
PubMed

Insights

Peroxynitrite causes muscle relaxation by activating ATP-sensitive potassium channels and potentially through cGMP pathways. Inhibiting poly(ADP-ribose)synthase did not affect this relaxant effect.

Area of Science:

  • Pharmacology
  • Physiology

Background:

  • Peroxynitrite (ONOO(-)) has been shown to induce relaxations in isolated rat anococcygeus muscle.
  • The precise mechanisms underlying this ONOO(-) induced relaxation require further investigation.

Purpose of the Study:

  • To elucidate the molecular mechanisms responsible for the relaxant effects of peroxynitrite in rat anococcygeus muscle.
  • To investigate the roles of ATP-sensitive potassium channels, guanylyl cyclase, and poly(ADP-ribose)synthase in ONOO(-) induced relaxation.

Main Methods:

  • Isolated rat anococcygeus muscle preparations were used.
  • The effects of peroxynitrite (ONOO(-)) on muscle relaxation were assessed in the presence of specific inhibitors.
  • Inhibitors included glibenclamide (K(+)(ATP) channel blocker) and ODQ (guanylyl cyclase inhibitor).
  • 3-aminobenzamide (poly(ADP-ribose)synthase inhibitor) was also used.

Main Results:

  • Peroxynitrite (0.03-1.0 mmol/l) induced significant muscle relaxations.
  • Glibenclamide and ODQ significantly reduced the ONOO(-) induced relaxations.
  • 3-aminobenzamide did not affect the relaxant response to ONOO(-) (1.0 mmol/l).

Conclusions:

  • Activation of ATP-sensitive potassium (K(+)(ATP)) channels is implicated in the relaxant responses to peroxynitrite.
  • cGMP signaling pathways may interact with K(+)(ATP) channels to mediate ONOO(-) induced relaxation.
  • Poly(ADP-ribose)synthase does not appear to play a significant role in this specific relaxant effect.

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