Extracellular signal-regulated kinase (ERK1/2) contributes to endotoxin-induced hyporeactivity via nitric oxide and prostacyclin production in rat aorta.
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.
Korkmaz
Belma
B
Department of Pharmacology, Faculty of Pharmacy, Mersin University, Mersin, Turkey.
Ozveren
Elif
E
Buharalioglu
Cuneyt Kemal
CK
Tunctan
Bahar
B
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology*; D004789:Enzyme Activation; D011464:Epoprostenol / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004731:Endotoxins; D014662:Vasoconstrictor Agents; D009569:Nitric Oxide; D011464:Epoprostenol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3