Batroxobin reduces intracellular calcium concentration and inhibits proliferation of vascular smooth muscle cells.
BACKGROUND
Batroxobin (BX), a serine protease used in defibrinogenation and thrombolysis, also has an effect on c-fos gene and growth factor. This study attempted to determine the effects of BX on the proliferation of vascular smooth muscle cells (VSMCs) and calcium metabolism.


METHODS
VSMCs were treated with BX at concentrations of 0.1, 0.3, or 1.0 mmol/L and cell numbers were determined at 0, 24, 48, and 72 hours. Intracellular calcium concentration ([Ca2+]i) was measured using direct fluorescence methods.


RESULTS
BX was found to suppress proliferation of VSMCs in a dose-dependent fashion with inhibition rates of 18% and 31% by 48 and 72 hours, respectively. In addition, BX decreases basal [Ca2+]i significantly. The basal level in untreated cells was 162.7 +/- 33.8 nmol/L, and decreased to 131.5 +/- 27.7 nmol/L, 128.3 +/- 28.5 nmol/L, and 125.6 +/- 34.3 nmol/L with the three concentrations of BX, respectively. Noradrenaline (NE)-induced [Ca2+]i stimulation was also attenuated by BX (0.1 mmol/L BX, 20% +/- 8% inhibition; 0.3 mmol/L BX, 54% +/- 11% inhibition; 1.0 mmol/L BX, 62% +/- 15% inhibition). The ability of NE to stimulate [Ca2+]i was attenuated in cultures in Ca(2+)-free medium, as was the ability of BX to blunt NE-induced stimulation.


CONCLUSIONS
These findings demonstrate that BX can effectively inhibit proliferation of VSMCs, probably by blocking the release and uptake of Ca2+, thus influencing [Ca2+]i.
Song
Qing-bin
QB
Department of Vascular Surgery, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
Wei
Min-jie
MJ
Duan
Zhi-quan
ZQ
Zhang
Hai-qiang
HQ
Schwartz
L B
LB
Xin
Shi-jie
SJ
D000818:Animals; D012103:Batroxobin / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D011817:Rabbits
D012103:Batroxobin; D002118:Calcium