The Inhibition Of L-Ca In ASMCs Involves In The Pathogenesis Of Vascular Hyporeactivity In Severe Shock

Shock is a complicated pathologic process which could be divided into two stages: reversible shock and irreversible shock (IS). Irreversible or severe shock is the final stage of shock, which is a life threatening situation with the therapeutic measures being ineffective. When it happens, vascular has responseless to vasoactive agonists, such as norepinephrine, Angiotensin II, epinephrine, and so on. Therefore, restitution of vasoreactivity provided us a new approach for the treatment of shock.Reviewing our results and results available in the literature it seems clear that potassium channels in ASMCs (BK_Ca, K_ATP ) are activated after 2 hours of hemorrhagic shock and increase the outward potassium currents, which leads to arteriolar smooth muscle cell membrane hyperpolarization and the changes of intracellular calcium dependent characteristic. This hyperpolarization might cause closing of voltage sensitive calcium channels, preferentially of the L-type, which modulation most excited and unexcited cells and is the major passage of calcium influx from extracellular. From Liu Jie's work we know that in the normal extracellular calcium enviroment, the increased intracellular calcium in ASMCs stimulated by NE(1mg/ml) is about 30% in the normal condition. But the intracellular calcium increase stimulated by NE in shock cells was only about half of normal cells. When the cells were put in zero extracellular calcium, the difference of calcium increased induced by NE between control and shock group is not as big as that in normal extracelluar calcium. It suggested that the reduction in intracellular calcium...