Receptor Mechanisms Underlying The Regulation By CCK-8 For LPS-induced NF-κB Expression In Vascular Endothelial Cells

Objective: Endotoxic shock induced by gram-negative bacteria lipopolysaccharide is a very dangerous pathologic process with mortality of 50%~80% and is characteristic of the disorders of blood vessels with depressed resistence of systemic circulation and continuous fall in mean arterial pressure. It has been well known that vascular endothelial cells (VEC) are one of the major target of endotoxin, and VEC are not only a mechanical and biological barriers of blood vessles, but also an important endocrine organ, participating in the regulation of vascular tone and blood flow distribution of organs via release of vasoactive substances such as nitric oxide (NO). Under the physiological circumstance, VEC produces the appropriated quantities of NO from the endothelial-type NO synthase (eNOS), playing as physiological regulation functions, whereas during the endotoxic shock, the upregulation of inducible NO synthase (iNOS) expression in VEC can be induced with enhanced activity of iNOS and the generation of large quantities of NO led to over-activation and dysfunctions of VEC, and resulted in the disorders of vascular regulations and circulation failure. The control of iNOS expression is at gene. The activation of NF- κB...