ABSTRACT
Objective To investigate the relationship of the beneficial effect of CsA on vascular reactivity to Rho-kinase,protein kinase C ( PKC) and mitochondrial permeability transition pore ( MPTP) in traumatic hemorrhagic shock rats. Methods With traumatic hemor-rhagic shock rats and hypoxia-treated vascular smooth muscle cells ( VSMCs) ,the role of Rho-kinase and PKC in CsA-regulating vascular re-activity following shock and their relationship to MPTP was observed. Meanwhile,the effects of CsA on inflammatory mediators including TNF-α, IL-1β and IL-6 were also studied. Results CsA significantly improved the vascular reactivity of superior mesenteric artery following hemor-rhagic shock. Rho-kinase inhibitor Y27632 significantly antagonized CsA-induced increase of vascular reactivity,while PKC inhibitor stauros-porine had no significant influences on the effects of CsA. Further studies showed that CsA and Rho-kinase agonist U46619 inhibited the o-pening of MPTP in hypoxia-treated VSMCs. In addition,shock induced a significant increase of TNF-αand IL-1β,but CsA did not show a sig-nificant inhibitory effect on their level. Conclusion CsA-induced restoration of vascular reactivity following traumatic hemorrhagic shock via inhibiting MPTP opening,and Rho-kinase participate in this process.