Epidermal growth factor induces vasoconstriction through the phosphatidylinositol 3-kinase-mediated mitogen-activated protein kinase pathway in hypertensive rats.
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.
Kim
Junghwan
J
Department of Physiology, College of Medicine, Institute of Biomedical Science and Technology, Konkuk University, Choongju, Korea.
Lee
Chang-Kwon
CK
Park
Hyo-Jun
HJ
Kim
Hyo Jin
HJ
So
Hyun Ha
HH
Lee
Keun Sang
KS
Lee
Hwan Myung
HM
Roh
Hui Yul
HY
Choi
Wahn Soo
WS
Park
Tae Kyu
TK
Kim
Bokyung
B
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*
D017673:Sodium Chloride, Dietary; D003900:Desoxycorticosterone; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D020928:Mitogen-Activated Protein Kinases