Peroxynitrite induces arteriolar smooth muscle cells membrane hyperpolarization with arteriolar hyporeactivity in rats.
Peroxynitrite (ONOO-) has been recently known to act as a potent cytotoxin during pathogenesis of various diseases. This study aimed to investigate the possible effect of ONOO- on the cremaster muscle arteriolar reactivity in response to noradrenaline and subsequently determined whether membrane hyperpolarization and potassium channel activation were involved in ONOO(-)-induced alteration of arteriolar reactivity. The results demonstrated that 1) ONOO- could decrease arteriolar reactivity in a time- and concentration-dependent manner with no significant alteration of arteriolar diameter; 2) Superfusion with 20 microM ONOO- over 40 minutes showed slight but not significant influence on the resting potential (Em) of arteriolar smooth muscle cells (ASMCs). However, ASMCs subjected to 50 or 100 microM ONOO- administration were significantly hyperpolarized. As control, treatment with 50 microM decomposed ONOO- or Kreb's solution had little effect on the Em of ASMCs; 3) ONOO(-)-induced arteriolar hyporeactivity could be greatly reversed by co-administration of KCl and partially by TEA. The above results indicated that membrane hyperpolarization and potassium channel activation were preferentially responsible for the reduction of cremaster muscle arteriolar reactivity after exposure to ONOO-.
Pan
Bing-Xing
BX
Key Lab for Shock and Microcirculation of PLA, Department of Pathophysiology, The First Military Medical University, Guangzhou 510515, PR China.
Zhao
Gui-Ling
GL
Huang
Xu-Liang
XL
Jin
Jian-Qiu
JQ
Zhao
Ke-Seng
KS
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D004396:Coloring Agents; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019789:Tetraethylammonium / Q000494:pharmacology
D004396:Coloring Agents; D007202:Indicators and Reagents; D030421:Peroxynitrous Acid; D019789:Tetraethylammonium; D011189:Potassium Chloride