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...

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Main Authors: Kim Junghwan, Lee Chang-Kwon, Park Hyo-Jun, Kim Hyo Jin, So Hyun Ha, Lee Keun Sang, Lee Hwan Myung, Roh Hui Yul, Choi Wahn Soo, Park Tae Kyu, Kim Bokyung
Format: Article
Language:English
Published: Elsevier 2006-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319344585
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spelling doaj-0069a0299d6d4f36a9aa42e8e704cbf42020-11-25T01:26:21ZengElsevierJournal of Pharmacological Sciences1347-86132006-01-011012135143Epidermal Growth Factor Induces Vasoconstriction Through the Phosphatidylinositol 3-Kinase-Mediated Mitogen-Activated Protein Kinase Pathway in Hypertensive RatsKim Junghwan0Lee Chang-Kwon1Park Hyo-Jun2Kim Hyo Jin3So Hyun Ha4Lee Keun Sang5Lee Hwan Myung6Roh Hui Yul7Choi Wahn Soo8Park Tae Kyu9Kim Bokyung10Department of Physiology, College of Medicine, Institute of Biomedical Science and Technology, College of Biomedical & Health Science, Konkuk University, Danwol-dong 322, Choongju 380-701, KoreaDepartment of Physiology, College of Medicine, Institute of Biomedical Science and Technology, College of Biomedical & Health Science, Konkuk University, Danwol-dong 322, Choongju 380-701, KoreaDepartment of Physiology, College of Medicine, Institute of Biomedical Science and Technology, College of Biomedical & Health Science, Konkuk University, Danwol-dong 322, Choongju 380-701, KoreaDepartment of Physiology, College of Medicine, Institute of Biomedical Science and Technology, College of Biomedical & Health Science, Konkuk University, Danwol-dong 322, Choongju 380-701, KoreaDepartment of Physiology, College of Medicine, Institute of Biomedical Science and Technology, College of Biomedical & Health Science, Konkuk University, Danwol-dong 322, Choongju 380-701, KoreaDepartment of Physiology, College of Medicine, Institute of Biomedical Science and Technology, College of Biomedical & Health Science, Konkuk University, Danwol-dong 322, Choongju 380-701, KoreaDepartment of Physiology, College of Medicine, Institute of Biomedical Science and Technology, College of Biomedical & Health Science, Konkuk University, Danwol-dong 322, Choongju 380-701, KoreaDepartment of Physiology, College of Medicine, Institute of Biomedical Science and Technology, College of Biomedical & Health Science, Konkuk University, Danwol-dong 322, Choongju 380-701, KoreaDepartment of Immunology, College of Medicine, Institute of Biomedical Science and Technology, College of Biomedical & Health Science, Konkuk University, Danwol-dong 322, Choongju 380-701, KoreaDepartment of Biotechnology, College of Biomedical & Health Science, Konkuk University, Danwol-dong 322, Choongju 380-701, KoreaDepartment of Physiology, College of Medicine, Institute of Biomedical Science and Technology, College of Biomedical & Health Science, Konkuk University, Danwol-dong 322, Choongju 380-701, Korea; Corresponding author. bkkim2@kku.ac.krAbstract.: 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-kinasehttp://www.sciencedirect.com/science/article/pii/S1347861319344585
collection DOAJ
language English
format Article
sources DOAJ
author Kim Junghwan
Lee Chang-Kwon
Park Hyo-Jun
Kim Hyo Jin
So Hyun Ha
Lee Keun Sang
Lee Hwan Myung
Roh Hui Yul
Choi Wahn Soo
Park Tae Kyu
Kim Bokyung
spellingShingle Kim Junghwan
Lee Chang-Kwon
Park Hyo-Jun
Kim Hyo Jin
So Hyun Ha
Lee Keun Sang
Lee Hwan Myung
Roh Hui Yul
Choi Wahn Soo
Park Tae Kyu
Kim Bokyung
Epidermal Growth Factor Induces Vasoconstriction Through the Phosphatidylinositol 3-Kinase-Mediated Mitogen-Activated Protein Kinase Pathway in Hypertensive Rats
Journal of Pharmacological Sciences
author_facet Kim Junghwan
Lee Chang-Kwon
Park Hyo-Jun
Kim Hyo Jin
So Hyun Ha
Lee Keun Sang
Lee Hwan Myung
Roh Hui Yul
Choi Wahn Soo
Park Tae Kyu
Kim Bokyung
author_sort Kim Junghwan
title Epidermal Growth Factor Induces Vasoconstriction Through the Phosphatidylinositol 3-Kinase-Mediated Mitogen-Activated Protein Kinase Pathway in Hypertensive Rats
title_short Epidermal Growth Factor Induces Vasoconstriction Through the Phosphatidylinositol 3-Kinase-Mediated Mitogen-Activated Protein Kinase Pathway in Hypertensive Rats
title_full Epidermal Growth Factor Induces Vasoconstriction Through the Phosphatidylinositol 3-Kinase-Mediated Mitogen-Activated Protein Kinase Pathway in Hypertensive Rats
title_fullStr Epidermal Growth Factor Induces Vasoconstriction Through the Phosphatidylinositol 3-Kinase-Mediated Mitogen-Activated Protein Kinase Pathway in Hypertensive Rats
title_full_unstemmed Epidermal Growth Factor Induces Vasoconstriction Through the Phosphatidylinositol 3-Kinase-Mediated Mitogen-Activated Protein Kinase Pathway in Hypertensive Rats
title_sort epidermal growth factor induces vasoconstriction through the phosphatidylinositol 3-kinase-mediated mitogen-activated protein kinase pathway in hypertensive rats
publisher Elsevier
series Journal of Pharmacological Sciences
issn 1347-8613
publishDate 2006-01-01
description 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
url http://www.sciencedirect.com/science/article/pii/S1347861319344585
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