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KMID : 0043320060290111024
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Archives of Pharmacal Research
2006 Volume.29 No. 11 p.1024 ~ p.1031
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Phorbol Ester-induced Contraction Through p38 Mitogen-activated Protein Kinase is Diminished in Aortas from DOCA-Salt Hypertensive Rats
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Lee Chang-Kwon
Kim Jung-Kwan
Won Kyung-Jong
Lee Hwan-Myung
Kim Hyo-Jin
Roh Hui-Yul
Park Hyo-Jun
Shin Hwa-Sup
Park Tae-Kyu
Kim Bo-Kyung
Lee Sang-Mok
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Abstract
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The role of mitogen-activated protein kinase (MAPK) in the decreased contractile response to phorbol ester in aortic smooth muscle strips from deoxycorticosterone acetate (DOCA)-salt hypertensive rats was examined. Norepinephrine (NE) evoked greater contractility in aortic strips from DOCA rats than in those of sham-operated rats. 12-Deoxyphorbol 13-isobutyrate (DPB) induced contraction in medium, which was diminished in strips from DOCA rats compared to sham-operated rats. Vasoconstrictions induced by these stimulants were inhibited by SB203580 and PD098059, inhibitors of p38 MAPK and extracellular signal-regulated kinase (ERK) 1/2, respectively, in both strips. The phosphorylation of p38 MAPK and ERK1/2 induced by NE was greater in strips from DOCA rats compared to those from sham-operated rats, and this phosphorylation was inhibited by the kinase inhibitors. DPB increased the phosphorylation of p38 MAPK and ERK1/2 in strips from both animals, and the increment of p38 MAPK phosphorylation by the stimulant was diminished in strips from DOCA rats compared to sham-operated rats. These findings suggest that the contraction evoked by DPB results from the activation of MAPKs in rat aortic smooth muscle and that the attenuated contractility by DPB in DOCA rat appears to be associated with diminished p38 MAPK activity.
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KEYWORD
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Phorbol ester, Mitogen-activated protein kinase, Hypertension, Vascular smooth muscle, Contraction
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