Related Experiment Video

Updated: May 13, 2026

Developing a Clinically Relevant Hemorrhagic Shock Model in Rats
08:14

Developing a Clinically Relevant Hemorrhagic Shock Model in Rats

Published on: March 22, 2024

Mitogen-activated protein kinases regulate vascular reactivity after hemorrhagic shock through myosin light chain

Guangming Yang1, Tao Li, Jing Xu

  • 1State Key Laboratory of Trauma, Burns and Combined Injury, Second Department of Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.

The Journal of Trauma and Acute Care Surgery
|March 21, 2013
PubMed
Abstract

Insights

Mitogen-activated protein kinases (MAPKs) regulate vascular reactivity during shock. Extracellular signal-regulated kinase (ERK) and p38 MAPK primarily act via specific pathways, while jun NH2-terminal kinase (JNK) may use other mechanisms.

Area of Science:

  • Physiology
  • Molecular Biology
  • Critical Care Medicine

Background:

  • Vascular hyporeactivity is a key feature of critical illnesses like shock and sepsis.
  • The precise molecular mechanisms underlying vascular hyporeactivity remain incompletely understood.

Purpose of the Study:

  • To investigate the roles of major mitogen-activated protein kinases (MAPKs) – extracellular signal-regulated kinase (ERK), p38 MAPK, and jun NH2-terminal kinase (JNK) – in vascular reactivity during shock.
  • To elucidate the mechanisms by which these MAPKs influence vascular tone, focusing on myosin light chain (MLC20) phosphorylation.

Main Methods:

  • Analysis of superior mesenteric arteries from rats subjected to hemorrhagic shock.
  • Assessment of MAPK activity and its impact on vascular reactivity, calcium sensitivity, and MLC20 phosphorylation.
  • Utilized specific inhibitors to delineate the roles of ERK, p38 MAPK, and JNK in Angiotensin II-stimulated responses.

Main Results:

  • ERK, p38 MAPK, and JNK activities were elevated in early shock and decreased in late shock.
  • Angiotensin II stimulation increased vascular reactivity, calcium sensitivity, and MLC20 phosphorylation, effects modulated by MAPK activity.
  • ERK and p38 MAPK were crucial for Angiotensin II-induced increases in calcium sensitivity and phosphorylation of downstream targets like CPI17, ILK, and ZIPK.

Conclusions:

  • MAPKs are integral to regulating vascular reactivity during shock.
  • ERK and p38 MAPK exert their effects predominantly through the ILK, ZIPK, and CPI17-mediated MLC20 phosphorylation pathway.
  • JNK's role in vascular reactivity during shock may involve mechanisms distinct from those of ERK and p38 MAPK.

More Related Videos

Fixed Volume or Fixed Pressure: A Murine Model of Hemorrhagic Shock16:31

Fixed Volume or Fixed Pressure: A Murine Model of Hemorrhagic Shock

Published on: June 6, 2011

Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function06:14

Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function

Published on: June 11, 2017

Related Concept Videos

Vascular Spasm01:16

Vascular Spasm

The vascular phase, also known as vasospasm, is the initial stage of hemostasis, crucial for preventing excessive bleeding when a blood vessel is injured. After a vessel is cut, nerves in the damaged area trigger pain and other sensory impulses. Simultaneously, the smooth muscles in the vessel wall contract, resulting in a vascular spasm. This contraction reduces the vessel's diameter at the injury site, slowing or stopping blood loss through the vessel wall. Vascular spasms typically last for...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Autoregulation of Blood Flow01:17

Autoregulation of Blood Flow

Autoregulation mechanisms are characterized by their inherent capacity for self-regulation without necessitating specific nervous stimulation or endocrine control. These mechanisms facilitate the adjustment of blood flow and, therefore, perfusion specific to each tissue region. This self-regulation encompasses chemical signals and myogenic controls.
Chemical Signaling in Autoregulation
Chemical signaling operates at the precapillary sphincter level, inciting either contraction or relaxation.
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...