BACKGROUND: Vascular hyporeactivity played an important role in many critical illness including shock or sepsis, but the mechanisms are incompletely understood. The objective of the present study was to investigate the roles of major mitogen-activated protein kinases (MAPKs extracellular signal-regulated kinase [ERK], p38 MAPK, and jun NH2-terminal kinase [JNK]) on vascular reactivity and the mechanisms.
METHODS: With superior mesenteric arteries from hemorrhagic shock rats, the role of p38 MAPK, ERK, and JNK in the regulation of vascular reactivity following shock and their relationship to myosin light chain (MLC20) phosphorylation–dependent pathway was observed.
RESULTS: ERK, p38 MAPK, and JNK activities in superior mesenteric arteries were increased at early shock and decreased at late shock. Stimulation of MAPKs with angiotensin II (AngII) increased the vascular reactivity, calcium sensitivity, and MLC20 phosphorylation. The increasing effect of AngII on vascular reactivity was antagonized by ERK, p38 MAPK, and JNK inhibitors, while the effect of AngII on calcium sensitivity was only blocked by ERK and p38 MAPK inhibitor, but not by JNK inhibitor. AngII increased the activity of protein kinase C–dependent phosphatase inhibitor of 17-kD (CPI17), integrin-linked kinase (ILK), and zipper-interacting protein kinase (ZIPK), The effect of AngII on CPI17 was blocked by ERK and p38 MAPK inhibitor, while the effect of AngII on ILK and ZIPK was only blocked by ERK inhibitor.
CONCLUSION: MAPKs participated in the regulation of vascular reactivity during shock. ERK and p38 MAPK is mainly through ILK, ZIPK, and CPI17-mediated MLC20 phosphorylation–dependent pathway, while JNK may be involved in the regulation of vascular reactivity by other mechanisms.
From the State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
Submitted: November 14, 2011, Revised: December 15, 2012, Accepted: December 19, 2012.
Address for reprints: Liangming Liu, MD, PhD, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Daping, Chongqing 400042, China; email: firstname.lastname@example.org.