Study On Effects Of Lobelia Chinensis Lour Alkaloid And Lobeline On Proliferative Human Umbilical Arterial Smooth Muscle Cells Induced By Endothelin-1

Vascular smooth muscle cells (VSMCs) proliferation and migration induced by various growth factors can develop a variety of pathological processes including atherosclerosis, hypertension and restenosis after balloon angioplasty. Consequently, inhibition of VSMCs proliferation represents a potentially important therapeutic strategy for the treatment of diseases such as atherosclerosis, hypertension and restenosis. It is well known that endothelin (ET), secreted by vascular endothelial cells (VEC), induces a prolonged vasoconstriction and enhances proliferation of VSMCs by activating c-fos and c-myc.ETs have strong affinities to biologic toxins such as snake venoms, scorpion venoms and Bee Venoms. Sarafotoxins (SRTXs), initially isolated from the venom of Atractaspis engaddensis, constitute a family of vasoactive peptides, which are structurally and functionally related to ETs. SRTXs and ETs display about 60% of amino acid sequence identity and identical C-terminus. Different studies performed on ETs have confirmed the crucial role played by the C-terminus, the two disulphide bridges, the amino and carboxy terminal groups, together with the carboxylic groups of Asp8 and Glu10, for their vasoconstrictor activity. These observations and results strongly suggest that these residues might form the 'common and basic' vasoconstrictor site onto the surface of SRTXs and ETs. SRTXs form with ETs a homogeneous family of potently vasoconstrictive isopeptides that act on the vascular system via identical G protein receptors and activate the IP₃, Ca²⁺, CaM pathway to modulate various biologic effects. These interesting relationships between ETs and SRTXs led us to investigate the effect of Chinese anti-snake venom herbal...