[Regulatory effect of protein kinase C and protein kinase G on calcium sensitivity of vascular smooth muscle cells following hemorrhagic shock].
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).


CONCLUSIONS
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.
Li
Tao
T
State Key Laboratory of Trauma, Burns and Combined Injury, Department 2, Research Institute of Surgery, Daping Hospital, the Third Military University, Chongqing 400042, China.
Liu
Liang-ming
LM
Liu
Jian-cang
JC
D000818:Animals; D002118:Calcium / Q000008:administration & dosage / Q000494:pharmacology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000503:physiopathology*; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012771:Shock, Hemorrhagic / Q000201:enzymology / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C; D002118:Calcium