Martentoxin, a large-conductance Ca(2+)-activated K(+) channel inhibitor, attenuated TNF-α-induced nitric oxide release by human umbilical vein endothelial cells.

Martentoxin, a 4,046 Da polypeptide toxin purified from the venom of the scorpion Buthus martensii Karsch, has been demonstrated to block large-conductance Ca(2+)-activated K(+) (BKCa) channels; however, its biological roles are still largely unknown. In the present study, we investigated the pharmacological effects of martentoxin on regulating the production of nitric oxide induced by TNF-α in human umbilical vein endothelial cells (HUVECs). We found that, 1, 10 and 100 µmol/L martentoxin decreased nitric oxide production by HUVECs exposed to 10 ng/mL TNF for 6, 12 and 24 hours. We further demonstrated that martentoxin inhibited the activity of iNOS and retarded the down-regulation of eNOS mRNA induced by TNF-α. Therefore, martentoxin could be a potential therapeutic agent for vascular diseases.