p38 Mitogen-Activated Protein Kinase Contributes to the Diminished Aortic Contraction by Endothelin-1 in DOCA-Salt Hypertensive Rats

DOI Web Site 被引用文献16件
  • Bokyung Kim
    From the Department of Physiology (B.K., J.K., Y.M.B., S.I.C.), College of Medicine, Konkuk University, Choongju, Korea; Department of Physiology (S.C.K.), College of Medicine, Kwandong University, Kangneung, Korea; Department of Pharmacology (J. Y. J., J.C.P., H.Y.A.), College of Medicine, Chungbuk National University, Cheongju, Korea.
  • Junghwan Kim
    From the Department of Physiology (B.K., J.K., Y.M.B., S.I.C.), College of Medicine, Konkuk University, Choongju, Korea; Department of Physiology (S.C.K.), College of Medicine, Kwandong University, Kangneung, Korea; Department of Pharmacology (J. Y. J., J.C.P., H.Y.A.), College of Medicine, Chungbuk National University, Cheongju, Korea.
  • Young M. Bae
    From the Department of Physiology (B.K., J.K., Y.M.B., S.I.C.), College of Medicine, Konkuk University, Choongju, Korea; Department of Physiology (S.C.K.), College of Medicine, Kwandong University, Kangneung, Korea; Department of Pharmacology (J. Y. J., J.C.P., H.Y.A.), College of Medicine, Chungbuk National University, Cheongju, Korea.
  • Sung I. Cho
    From the Department of Physiology (B.K., J.K., Y.M.B., S.I.C.), College of Medicine, Konkuk University, Choongju, Korea; Department of Physiology (S.C.K.), College of Medicine, Kwandong University, Kangneung, Korea; Department of Pharmacology (J. Y. J., J.C.P., H.Y.A.), College of Medicine, Chungbuk National University, Cheongju, Korea.
  • Seong C. Kwon
    From the Department of Physiology (B.K., J.K., Y.M.B., S.I.C.), College of Medicine, Konkuk University, Choongju, Korea; Department of Physiology (S.C.K.), College of Medicine, Kwandong University, Kangneung, Korea; Department of Pharmacology (J. Y. J., J.C.P., H.Y.A.), College of Medicine, Chungbuk National University, Cheongju, Korea.
  • Jin Y Jung
    From the Department of Physiology (B.K., J.K., Y.M.B., S.I.C.), College of Medicine, Konkuk University, Choongju, Korea; Department of Physiology (S.C.K.), College of Medicine, Kwandong University, Kangneung, Korea; Department of Pharmacology (J. Y. J., J.C.P., H.Y.A.), College of Medicine, Chungbuk National University, Cheongju, Korea.
  • Jung -C. Park
    From the Department of Physiology (B.K., J.K., Y.M.B., S.I.C.), College of Medicine, Konkuk University, Choongju, Korea; Department of Physiology (S.C.K.), College of Medicine, Kwandong University, Kangneung, Korea; Department of Pharmacology (J. Y. J., J.C.P., H.Y.A.), College of Medicine, Chungbuk National University, Cheongju, Korea.
  • Hee Y. Ahn
    From the Department of Physiology (B.K., J.K., Y.M.B., S.I.C.), College of Medicine, Konkuk University, Choongju, Korea; Department of Physiology (S.C.K.), College of Medicine, Kwandong University, Kangneung, Korea; Department of Pharmacology (J. Y. J., J.C.P., H.Y.A.), College of Medicine, Chungbuk National University, Cheongju, Korea.

抄録

<jats:p>We investigated whether the diminished contractile responsiveness to endothelin-1 (ET-1) is associated with the altered activation of mitogen-activated protein kinase (MAPK) in aortic smooth muscles from deoxycorticosterone acetate (DOCA)-salt hypertensive rats. ET-1 dose-dependently increased contractions in aortic smooth muscle strips, and the contractions were significantly attenuated in tissues from DOCA-salt hypertensive rats compared with those from sham-operated rats. The phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was elevated by ET-1, with the magnitude and time-course being similar between strips. Although ET-1 also increased the phosphorylation of p38 MAPK in both strips, the increment was markedly lower in the strips from DOCA-salt hypertensive rats compared with sham-operated controls. 5-Hydroxytryptamine (5-HT) increased vascular contraction and phosphorylation of both MAPK isoforms; these were greater in DOCA-salt hypertensive rats than in sham-operated rats. ET-1 also increased the phosphorylation of caldesmon, an actin-binding protein, in sham-operated and DOCA-salt hypertensive rats. However, the increment was markedly lower in the strips from DOCA-salt hypertensive rats compared with sham-operated controls. The phosphorylation of MAPK isoforms and caldesmon elevated by ET-1 was inhibited by PD098059, an inhibitor of ERK1/2 kinase, and SB203580, an inhibitor of p38 MAPK, respectively. These results suggest that ET-1 and 5-HT induce contraction by activating the MAPK pathway in rat aortic smooth muscle and that the diminished responsiveness to ET-1 in the DOCA-salt hypertensive rat may be, in part, mediated by the decrease of caldesmon phosphorylation after the decreased activation of p38 MAPK.</jats:p>

収録刊行物

  • Hypertension

    Hypertension 43 (5), 1086-1091, 2004-05

    Ovid Technologies (Wolters Kluwer Health)

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