title: Epidermal growth factor induces vasoconstriction through the phosphatidylinositol 3-kinase-mediated mitogen-activated protein kinase pathway in hypertensive rats.
abstract: We investigated whether increased contractile responsiveness to epidermal growth factor (EGF) is associated with altered activation of mitogen-activated protein kinase (MAPK) in the aortic smooth muscle of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. EGF induced contraction and MAPK activity in aortic smooth muscle strips, which were significantly increased in tissues from the DOCA-salt hypertensive rats compared with those from sham-operated rats. AG1478, PD98059, and LY294002, inhibitors of EGF receptor (EGFR) tyrosine kinase, MAPK/extracellular signal-regulated kinase (ERK) kinase, and phosphatidylinositol 3-kinase (PI3K), respectively, inhibited the contraction and the activity of ERK1/2 that were elevated by EGF. Y27632 and GF109203X, inhibitors of Rho kinase and protein kinase C, respectively, attenuated EGF-induced contraction, with no diminution of ERK1/2 activity. Although EGF also elevated the activity of EGFR tyrosine kinase in both sham-operated and DOCA-salt hypertensive rats, the expression and the magnitude of activation did not differ between strips. These results strongly suggest that EGF induces contraction by the activation of ERK1/2, which is regulated by the PI3K pathway in the aortic smooth muscle of DOCA-salt hypertensive rats.
authors.affiliation: Department of Physiology, College of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Choongju, Korea.
authors.forename: Junghwan
authors.initials: J
authors.lastname: Kim
authors.forename: Chang-Kwon
authors.initials: CK
authors.lastname: Lee
authors.forename: Hyo-Jun
authors.initials: HJ
authors.lastname: Park
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hyun Ha
authors.initials: HH
authors.lastname: So
authors.forename: Keun Sang
authors.initials: KS
authors.lastname: Lee
authors.forename: Hwan Myung
authors.initials: HM
authors.lastname: Lee
authors.forename: Hui Yul
authors.initials: HY
authors.lastname: Roh
authors.forename: Wahn Soo
authors.initials: WS
authors.lastname: Choi
authors.forename: Tae Kyu
authors.initials: TK
authors.lastname: Park
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D003900:Desoxycorticosterone / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000633:toxicity; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D017673:Sodium Chloride, Dietary; D003900:Desoxycorticosterone; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases