title: A role for angiotensin II in the activation of extracellular signal-regulated kinases in the liver during hemorrhagic shock.
abstract: Hemorrhagic shock (HS) is a complex process that initiates a global stress response. However, the earliest signaling pathways responsible for initiating this response remain unidentified. We have investigated the involvement of the extracellular signal-regulated kinases (ERK 1/2; also known as p42/44) and their activation in the liver by angiotensin II in the early signal transduction after HS. Hemorrhage of mice to 25 mmHg for 30 min was associated with the activation of ERK 1/2 in the liver, and this was accompanied by a 6.7-fold elevation of circulating angiotensin II levels. Similar results were obtained in rats. Both the angiotensin II levels and ERK 1/2 phosphorylation were suppressed by administration of an angiotensin-converting enzyme inhibitor peptide. Plasma from shocked rats, but not shocked rats treated with the angiotensin-converting enzyme inhibitor, increased ERK 1/2 phosphorylation in cultured hepatocytes. Together, these data suggest that angiotensin II is an important stimulus for ERK 1/2 activation in the liver during HS.
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D004789:Enzyme Activation; D022781:Hepatocytes / Q000201:enzymology; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000097:blood / Q000378:metabolism*
chemical_list: D003470:Culture Media; D000804:Angiotensin II; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases