Mobilization of intracellular calcium by peroxynitrite in arteriolar smooth muscle cells from rats

Redox Rep. 2004;9(1):49-55. doi: 10.1179/135100004225003914.


The present study was designed to investigate the possible effects of peroxynitrite (ONOO(-)) on the intracellular calcium concentration ([Ca(2+)](i)) of mesenteric arteriolar smooth muscle cells (ASMCs), and to reveal the underlying mechanisms by using fluorescence imaging analysis. The results showed that ONOO(-) could exert a concentration- and time-dependent but also a dual effect on [Ca(2+)](i). Bolus administration with a low concentration of ONOO(-) (25 microM) decreased [Ca(2+)](i), whereas higher concentrations (50 or 100 microM) increased [Ca(2+)](i) persistently. Further experiments demonstrated that pretreatment of ASMCs with calcium-free medium completely abolished [Ca(2+)](i) increase by 100 microM ONOO(-). Additionally, nifedipine, an antagonist of selective L-type voltage-gated calcium channels (VGCCs), delayed the [Ca(2+)](i) response to ONOO(-), and ryanodine, an inhibitor of intracellular calcium release from the sarcoplasmic reticulum, effectively antagonized [Ca(2+)](i) increase during the late stage of ONOO(-) exposure. Furthermore, [Ca(2+)](i) alteration by ONOO(-) appeared to be intimately associated with the subsequent membrane potential changes. Although the mechanisms by which ONOO(-) alters [Ca(2+)](i) are complex, we conclude that a series of variables such as external calcium influx, activation of VGCCs, intracellular calcium release, and membrane potential changes are involved. The decrease of [Ca(2+)](i) in ASMCs by a low concentration of ONOO(-) may participate in the pathogenesis of low vasoreactivity in shock, and the increase of [Ca(2+)](i) by high concentrations of ONOO(-) may lead to calcium overload with cellular injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterioles / cytology*
  • Calcium / metabolism*
  • Calcium / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism*
  • Nifedipine / pharmacology
  • Peroxynitrous Acid / agonists
  • Peroxynitrous Acid / antagonists & inhibitors
  • Peroxynitrous Acid / pharmacology*
  • Rats
  • Rats, Wistar
  • Ryanodine / pharmacology
  • Time Factors


  • Calcium Channel Blockers
  • Peroxynitrous Acid
  • Ryanodine
  • Nifedipine
  • Calcium