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(Hypertension. 2004;43:1086.)
© 2004 American Heart Association, Inc.

Scientific Contributions

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

Bokyung Kim; Junghwan Kim; Young M. Bae; Sung I. Cho; Seong C. Kwon; Jin Y Jung; Jung -C. Park; 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.

Correspondence to Dr Hee Y. Ahn, Department of Pharmacology, College of Medicine, Chungbuk National University, Cheongju 361-763, Korea. E-mail hyahn{at}chungbuk.ac.kr

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.

Key Words: endothelin • hypertension • vasoconstriction • deoxycorticosterone • protein kinases

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