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Severe trauma / shock decompensated often appear low reactivity of the blood vessels, mainly as reduce systemic vascular response to vasoconstrictor and vasodilator substances or reaction, the present study found that it may be associated with increased NO levels, vascular smooth muscle cells ( VSMC) potassium, calcium channel dysfunction induced by NE, Ang-II, endothelin receptor desensitization and membrane hyperpolarization, but inhibition of NO improve potassium, calcium channels, and restore receptor sensitivity, and cell membrane polarization state and can not be completely reversed vascular hyporeactivity shock. Recent studies have found that severe trauma, shock and cardiac myocyte calcium overload and calcium desensitization (calcium desensitization, reduce cardiac myocyte contractile protein calcium sensitivity, contractile force / calcium ratio decreased) phenomenon exists, resulting in myocardial cells to increased The the traditional cardiac drugs intracellular calcium ion concentration [Ca 2 ] i as the main mechanism of action is not sensitive. Previous studies in our laboratory found that calcium overload phenomenon also exists in vascular smooth muscle cells after shock Although the shock is not low intracellular calcium of vascular smooth muscle cells, vascular reactivity is still low, speculated shock, vascular smooth muscle cells may exist of calcium desensitization, calcium desensitization may play an important role in the occurrence of the shock vascular hyporeactivity. In this respect at home and abroad is still a lack of research. This purpose in this study using rat model of hemorrhagic shock, superior mesenteric artery for study, research after hemorrhagic shock in the rat vascular smooth muscle calcium desensitization, calcium desensitization in rats with hemorrhagic shock vascular hyporeactivity the role of Rho-kinase, PKC and PKG on calcium sensitivity of the role and possible mechanisms. Main method: hemorrhagic shock in rat mesenteric artery (SMA), the use of in vitro vascular ring tension measurement techniques, with a vascular ring of gradient concentrations of norepinephrine (NE) contractile force reflect vascular reactivity, spent polarization contractile force of the state (120 mmol / LK ) vascular ring of the gradient of the concentration of Ca 2 reflect vascular calcium sensitivity. Experiments into three parts, the first part of the experiment the observed hemorrhagic shock hyporesponsiveness vascular calcium sensitivity decreases, as well as by observing the calcium sensitivity adjustment agent angiotensin Ⅱ (Ang-Ⅱ), insulin and Rho-kinase specific antagonistic agent fasudil can be adjusted by adjusting the calcium sensitivity of vascular reactivity, in order to confirm the role of calcium desensitization in the formation of the shock vascular hyporeactivity. The second part of the observation of the agonist Ang-Ⅱ antagonist fasudil Rho-kinase, PKC activator PMA and the antagonists staurosporine, 8Br-cGMP PKG agonist and antagonist KT-5823 on hemorrhagic shock vascular calcium sensitivity to understand the role of Rho-kinase, PKC, and PKG on calcium sensitivity. The third part of the observed the MLCP antagonist Calyculin A Rho-kinase, PKC, PKG regulation hemorrhagic shock vascular calcium sensitivity, and to explore the possible mechanism of the Rho-kinase, PKC, and PKG regulation of calcium sensitivity.
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