p38 Mitogen-Activated Protein Kinase Regulates Vasoconstriction in Spontaneously Hypertensive Rats

We investigated whether p42/p44 mitogen-activated protein kinase (MAPK) and/or p38 MAPK participates in the regulation of vascular smooth muscle contraction by endothelin-1 (ET-1) in Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR). ET-1 (10 nM) induced a sustained contraction in WKY...

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Main Authors: Seongchun Kwon, Lian Hua Fang, Bokyung Kim, Tae-Seon Ha, Sang Jin Lee, Hee Yul Ahn
Format: Article
Language:English
Published: Elsevier 2004-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319324454
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author Seongchun Kwon
Lian Hua Fang
Bokyung Kim
Tae-Seon Ha
Sang Jin Lee
Hee Yul Ahn
author_facet Seongchun Kwon
Lian Hua Fang
Bokyung Kim
Tae-Seon Ha
Sang Jin Lee
Hee Yul Ahn
author_sort Seongchun Kwon
collection DOAJ
description We investigated whether p42/p44 mitogen-activated protein kinase (MAPK) and/or p38 MAPK participates in the regulation of vascular smooth muscle contraction by endothelin-1 (ET-1) in Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR). ET-1 (10 nM) induced a sustained contraction in WKY and SHR aortas. PD98059 (100 μM), an inhibitor of p42/p44 MAPK kinase, partially attenuated the ET-1-induced contraction in WKY and SHR. However, SB203580 (10 μM), an inhibitor of p38 MAPK, relaxed the ET-1-induced contraction to the resting levels in SHR, but not in WKY. ET-1 (10 nM) increased phosphorylation of both p42/p44 MAPK and p38 MAPK in WKY and SHR. However, in SHR, p38 MAPK phosphorylation in response to ET-1 stimulation was increased more than in WKY. PD98059 (100 μM) and SB203580 (10 μM) abolished the phosphorylation of p42/p44 MAPK and p38 MAPK in response to ET-1 stimulation in WKY and SHR, respectively. On the other hand, SB203580 (10 μM) did not affect myosin light chain (MLC) phosphorylation in response to ET-1 (10 nM) stimulation in WKY and SHR. From these results, it is concluded that p42/p44 MAPK and/or p38 MAPK partially regulates the ET-1-induced vasoconstriction in WKY. However, p38 MAPK, rather than p42/p44 MAPK, activation plays an important role for the maintenance of ET-1-induced vasoconstriction in SHR through a MLC phosphorylation-independent pathway. Keywords:: p38 mitogen-activated protein kinase, endothelin, contraction, spontaneously hypertensive rat
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spelling doaj.art-55cc0ffb540e4648b294f798847933662022-12-21T22:38:16ZengElsevierJournal of Pharmacological Sciences1347-86132004-01-01952267272p38 Mitogen-Activated Protein Kinase Regulates Vasoconstriction in Spontaneously Hypertensive RatsSeongchun Kwon0Lian Hua Fang1Bokyung Kim2Tae-Seon Ha3Sang Jin Lee4Hee Yul Ahn5Department of Physiology, College of Medicine, Kwandong University, Kangnung 210-701, KoreaDepartment of Pharmacology, College of Medicine, Chungbuk University, Cheongju 361-763, KoreaDepartment of Physiology, College of Medicine, Konkuk University, Choongju 380-701, KoreaDepartment of Pediatrics, College of Medicine, Chungbuk University, Cheongju 361-763, KoreaDepartment of Physiology, College of Medicine, Chungbuk University, Cheongju 361-763, KoreaDepartment of Pharmacology, College of Medicine, Chungbuk University, Cheongju 361-763, Korea; Corresponding author. FAX: +82 43 272 1603 E-mail: hyahn@chungbuk.ac.krWe investigated whether p42/p44 mitogen-activated protein kinase (MAPK) and/or p38 MAPK participates in the regulation of vascular smooth muscle contraction by endothelin-1 (ET-1) in Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR). ET-1 (10 nM) induced a sustained contraction in WKY and SHR aortas. PD98059 (100 μM), an inhibitor of p42/p44 MAPK kinase, partially attenuated the ET-1-induced contraction in WKY and SHR. However, SB203580 (10 μM), an inhibitor of p38 MAPK, relaxed the ET-1-induced contraction to the resting levels in SHR, but not in WKY. ET-1 (10 nM) increased phosphorylation of both p42/p44 MAPK and p38 MAPK in WKY and SHR. However, in SHR, p38 MAPK phosphorylation in response to ET-1 stimulation was increased more than in WKY. PD98059 (100 μM) and SB203580 (10 μM) abolished the phosphorylation of p42/p44 MAPK and p38 MAPK in response to ET-1 stimulation in WKY and SHR, respectively. On the other hand, SB203580 (10 μM) did not affect myosin light chain (MLC) phosphorylation in response to ET-1 (10 nM) stimulation in WKY and SHR. From these results, it is concluded that p42/p44 MAPK and/or p38 MAPK partially regulates the ET-1-induced vasoconstriction in WKY. However, p38 MAPK, rather than p42/p44 MAPK, activation plays an important role for the maintenance of ET-1-induced vasoconstriction in SHR through a MLC phosphorylation-independent pathway. Keywords:: p38 mitogen-activated protein kinase, endothelin, contraction, spontaneously hypertensive rathttp://www.sciencedirect.com/science/article/pii/S1347861319324454
spellingShingle Seongchun Kwon
Lian Hua Fang
Bokyung Kim
Tae-Seon Ha
Sang Jin Lee
Hee Yul Ahn
p38 Mitogen-Activated Protein Kinase Regulates Vasoconstriction in Spontaneously Hypertensive Rats
Journal of Pharmacological Sciences
title p38 Mitogen-Activated Protein Kinase Regulates Vasoconstriction in Spontaneously Hypertensive Rats
title_full p38 Mitogen-Activated Protein Kinase Regulates Vasoconstriction in Spontaneously Hypertensive Rats
title_fullStr p38 Mitogen-Activated Protein Kinase Regulates Vasoconstriction in Spontaneously Hypertensive Rats
title_full_unstemmed p38 Mitogen-Activated Protein Kinase Regulates Vasoconstriction in Spontaneously Hypertensive Rats
title_short p38 Mitogen-Activated Protein Kinase Regulates Vasoconstriction in Spontaneously Hypertensive Rats
title_sort p38 mitogen activated protein kinase regulates vasoconstriction in spontaneously hypertensive rats
url http://www.sciencedirect.com/science/article/pii/S1347861319324454
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