Mobilization of intracellular calcium by peroxynitrite in arteriolar smooth muscle cells from rats.
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.
Pan
Bing-Xing
BX
Department of Pathophysiology, First Military Medical University, Guangzhou, People's Republic of China.
Zhao
Gui-Ling
GL
Huang
Xu-Liang
XL
Zhao
Ke-Seng
KS
D000818:Animals; D001160:Arterioles / Q000166:cytology*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D013997:Time Factors
D002121:Calcium Channel Blockers; D030421:Peroxynitrous Acid; D012433:Ryanodine; D009543:Nifedipine; D002118:Calcium