title: Phorbol ester-induced contraction through p38 mitogen-activated protein kinase is diminished in aortas from DOCA-salt hypertensive rats.
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 Ca2+-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 Ca2+-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.
authors.affiliation: Department of Physiology, College of Medicine, Konkuk University, Chungju 380-701, Korea.
authors.forename: Chang-Kwon
authors.initials: CK
authors.lastname: Lee
authors.forename: Junghwan
authors.initials: J
authors.lastname: Kim
authors.forename: Kyung-Jong
authors.initials: KJ
authors.lastname: Won
authors.forename: Hwan Myung
authors.initials: HM
authors.lastname: Lee
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Hui Yul
authors.initials: HY
authors.lastname: Roh
authors.forename: Hyo-Jun
authors.initials: HJ
authors.lastname: Park
authors.forename: Hwa-Sup
authors.initials: HS
authors.lastname: Shin
authors.forename: Tae-Kyu
authors.initials: TK
authors.lastname: Park
authors.forename: Bokyung
authors.initials: B
authors.lastname: Kim
authors.forename: Sang-Mok
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003900:Desoxycorticosterone; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D010703:Phorbol Esters / Q000494:pharmacology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D010703:Phorbol Esters; D011725:Pyridines; D003900:Desoxycorticosterone; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one