Objective: To observe the effect of protein kinase C (PKC) and protein kinase G (PKG) on calcium desensitization following hemorrhagic shock in rats.
Methods: The model of hemorrhagic shock was replicated by blood letting and maintaining mean arterial pressure at 40 mm Hg (1 mm Hg=0.133 kPa) for 2 hours. The superior mesenteric artery (SMA) in hemorrhagic shock rats was adopted to assay the calcium sensitivity via observing the contraction initiated by calcium under depolarizing conditions (120 mmol/L K(+)) with isolated organ perfusion system. Meanwhile, the effects of the PMA (PKC agonist), staurosporine (PKC inhibitor), 8Br-cGMP (PKG agonist) and KT-5823 (PKG inhibitor) on calcium sensitivity and the changes in PKC and PKG activities in SMA were observed following hemorrhagic shock.
Results: The calcium sensitivity of SMA following hemorrhagic shock was significantly decreased, and the dose-effect curve shifted to the right significantly, maximum energy (Emax) decreased significantly at 2 hours following shock (all P<0.01). The PMA (1 x 10(-7) mol/L) and KT-5823 (1x10(-6) mol/L) significantly increased hemorrhagic shock-induced decrease in calcium sensitivity (P<0.05 or P<0.01). Staurosporine (1 x 10(-7) mol/L) and 8Br-cGMP (1 x 10(-4) mol/L) further decreased calcium sensitivity after shock (P<0.05 or P<0.01). The activity of PKC was decreased and PKG activity was increased 2 hours following shock (P<0.05 and P<0.01), and was positively and negatively correlated with calcium sensitivity of SMA, respectively (both P<0.01).
Conclusion: PKC and PKG take part in the regulation of calcium sensitivity following hemorrhagic shock. PKC up-regulates calcium sensitivity, and PKG down-regulates calcium sensitivity in vascular smooth muscle cells following hemorrhagic shock.