Extracellular Signal-Regulated Kinase (ERK1/2) Contributes to Endotoxin-Induced Hyporeactivity via Nitric Oxide and Prostacyclin Production in Rat Aorta
Year: 2006
Type: article
Abstract: This study was conducted to determine if mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase (ERK1/2) contribute to endotoxin-induced vascular hyporeactivity via nitric oxide (NO) and/or prostacyclin (PGI(2)) production in the rat isolated thoracic aorta. Incubation of endothelium-intact rings with endotoxin (100 microg/ml) for 4 h decreased the E(max) value and increased the EC(50) value of norepinephrine. The endotoxin-induced increase in the EC(50) value of norepinephrine was decreased by phenylene-1,3-bis[ethane-2-isothiourea] dihydrobromide (1,3-PBIT), a selective inducible NO synthase inhibitor, and U0126, a selective inhibitor of ERK1/2 phosphorylation by MAPK kinase. The endotoxin-induced decrease in the E(max) value of norepinephrine was reversed by 1,3-PBIT and further decreased by U0126. 1,3-PBIT and U0126 decreased the endotoxin-induced increase in the tissue nitrite and 6-keto-PGF(1)(alpha) levels. These data suggest that events related to the activation of ERK1/2 contribute to the endotoxin-induced hyporeactivity by increasing NO and PGI(2) production.
Source: Pharmacology
DOI: 10.1159/000095962
Institution: Mersin Üniversitesi
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2016899148