| After severe trauma or shock, including hemorrhagic, endotoxic and septic shock, vascular reactivity to vasoconstrictors and vasodilators is greatly reduced. Previous studies showed that it may be related to the functional disorder of the K+ and Ca2+ channels in vascular smooth muscle cell (VSMC), or the hyperpolarization of cell membrane. However, recovering the function of the K+ and Ca2+ channels and polarization state of the cell membrane cannot restore the vascular reactivity completely. Our previous study showed that calcium overload and calcium desensitization (the decrease of force/Ca2+ ratio) coexisted in the myocardium cell following severe trauma or shock, which resulted in the less reactivity of the myocardium cell to the traditional cardiotonics which increased the intracellular calcium concentration ([Ca2+]i). In addition, calcium overload was also found in VSMC following shock, calcium desensitization existed in VSMC following hemorrhagic shock, and calcium desensitization played an important role in vascular hyporeactivity in our previous studies. Rho kinase took part in the regulation of calcium sensitivity of vascular smooth muscle. But whether Rho kinase took part in the regulation of vascular reactivity following hemorrhagic shock and its mechanism are unclear. To elucidate this problem we used hemorrhagic shock model of rats to investigate the effects of Rho kinase on vascular reactivity following hemorrhagic shock and its mechanism.Methods:The experiments were conducted in three parts. In the first part, we observed the role of Rho kinase in the development of vascular hyporeactivity following hemorrhagic shock in rats. Superior mesenteric artery (SMA) from rats at different time after shock (shock 0h, 30min, 1h and 2h) was adopted to assay the vascular reactivity and calcium sensitivity via observing the contraction initiated by norepinephrine(NE) and Ca2+ under depolarizing conditions (120mmol/L K+) with isolated organ perfusion system. Rho kinase activity in... |
PDF Full Text Request