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Phorbol Ester-induced Contraction Through p38 Mitogen-activated Protein Kinase is Diminished in Aortas from DOCA-Salt Hypertensive Rats  

Lee, Chang-Kwon (Department of Physiology, College of Medicine, Konkuk University)
Kim, Jung-Kwan (Department of Physical Therapy, College of Natural Science, Yongin University)
Won, Kyung-Jong (Department of Physiology, College of Medicine, Konkuk University)
Lee, Hwan-Myung (Department of Physiology, College of Medicine, Konkuk University)
Kim, Hyo-Jin (Department of Physiology, College of Medicine, Konkuk University)
Roh, Hui-Yul (Department of Physiology, College of Medicine, Konkuk University)
Park, Hyo-Jun (Department of Physiology, College of Medicine, Konkuk University)
Shin, Hwa-Sup (Division of Life Science, College of Biomedical and Health Science, Konkuk University)
Park, Tae-Kyu (Division of Life Science, College of Biomedical and Health Science, Konkuk University)
Kim, Bo-Kyung (Department of Physiology, College of Medicine, Konkuk University)
Lee, Sang-Mok (Department of Veterinary Physiology, College of Veterinary Medicine, Konkuk University)
Publication Information
Archives of Pharmacal Research / v.29, no.11, 2006 , pp. 1024-1031 More about this Journal
Abstract
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 $Ca^{2+}-free$ 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 $Ca^{2+}-independent$ 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.
Keywords
Phorbol ester; Mitogen-activated protein kinase; Hypertension; Vascular smooth muscle; Contraction;
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