Effects of ischemic preconditioning on vascular reactivity and calcium sensitivity after hemorrhagic shock and their relationship to the RhoA–Rho-kinase pathway in rats.
We investigated the effect of ischemic preconditioning (IPC) on vascular reactivity and calcium sensitivity after hemorrhagic shock and its relationship to the RhoA–Rho-kinase pathway. Using hemorrhagic-shock rats (40 mm Hg for 3 hours) and isolated rings of the superior mesenteric artery (SMA), the effects of IPC (abdominal aorta occlusion applied 2 hours before shock) on the pressor effect of norepinephrine (3 μg/kg), vascular reactivity and calcium sensitivity of SMA, and the activity and role of RhoA and Rho-kinase were investigated. IPC with 1-minute occlusion plus 5-minute loosening of aneurysm clips thrice significantly increased survival time and prevalence of survival at 24 hours of hemorrhagic-shock rats. This IPC condition also significantly increased the pressor response of norepinephrine and significantly improved the vascular reactivity and calcium sensitivity of the SMA. The activity of Rho-kinase and RhoA in the SMA decreased after hemorrhagic shock, but increased after IPC. Y-27632 (Rho-kinase antagonist) and C3 Transferase (RhoA antagonist) significantly decreased IPC-induced increase in vascular reactivity and calcium sensitivity. These results suggested that IPC can improve shock-induced vascular hyporeactivity and calcium desensitization. The RhoA–Rho-kinase pathway played an important part in this process. These findings suggested that the RhoA–Rho-kinase pathway may be a potential target to treat vascular hyporeactivity in severe trauma, shock, or multiple-organ dysfunction syndrome.
State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Daping, Chongqing 400042, China.
Yi
Y
Hu
Tao
T
Li
Xiao Feng
XF
Tang
Ken
K
Chen
Liangming
L
Liu
D000577:Amides / Q000494:pharmacology; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology* / Q000378:metabolism; D002118:Calcium / Q000502:physiology*; D019194:Ischemic Preconditioning / Q000379:methods*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000201:enzymology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000502:physiology*
D000577:Amides; D011725:Pyridines; C066737:RHOA protein, human; C108830:Y 27632; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein; D002118:Calcium