Epidermal Growth Factor Induces Vasoconstriction Through the Phosphatidylinositol 3-Kinase-Mediated Mitogen-Activated Protein Kinase Pathway in Hypertensive Rats

• Main Authors: Kim Junghwan (Author), Lee Chang-Kwon (Author), Park Hyo-Jun (Author), Kim Hyo Jin (Author), So Hyun Ha (Author), Lee Keun Sang (Author), Lee Hwan Myung (Author), Roh Hui Yul (Author), Choi Wahn Soo (Author), Park Tae Kyu (Author), Kim Bokyung (Author)
• Format: Book
• Published: Elsevier, 2006-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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. Keywords:: epidermal growth factor, hypertension, vasoconstriction, mitogen-activated protein kinase, phosphatidylinositol 3-kinase

Item Description

1347-8613
10.1254/jphs.FP0060021