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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Elsevier
2004-01-01
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Series: | Journal of Pharmacological Sciences |
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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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issn | 1347-8613 |
language | English |
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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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