Published Online
on March 29, 2004

A more recent version of this article appeared on May 1, 2004

This Article Full Text (PDF) All Versions of this Article: 43/5/1086    most recent 01.HYP.0000125995.85427.fdv1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kim, B. Articles by Ahn, H. Y. Search for Related Content PubMed PubMed Citation Articles by Kim, B. Articles by Ahn, H. Y. Related Collections Hypertension - basic studies

Submitted on October 2, 2003
Revised on October 31, 2003

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; and 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.

^* To whom correspondence should be addressed. E-mail: hyahn{at}chungbuk.ac.kr.

Abstract--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

This article has been cited by other articles:

				U. Sen, N. Tyagi, P. K. Patibandla, W. L. Dean, S. C. Tyagi, A. M. Roberts, and D. Lominadze Fibrinogen-induced endothelin-1 production from endothelial cells Am J Physiol Cell Physiol, April 1, 2009; 296(4): C840 - C847. [Abstract] [Full Text] [PDF]

				X.-K. Tong and E. Hamel Transforming Growth Factor-beta1 Impairs Endothelin-1-Mediated Contraction of Brain Vessels by Inducing Mitogen-Activated Protein (MAP) Kinase Phosphatase-1 and Inhibiting p38 MAP Kinase Mol. Pharmacol., December 1, 2007; 72(6): 1476 - 1483. [Abstract] [Full Text] [PDF]

				E. Y. Lai, P. Martinka, M. Fahling, R. Mrowka, A. Steege, A. Gericke, M. Sendeski, P.B. Persson, A. E. G. Persson, and A. Patzak Adenosine Restores Angiotensin II-Induced Contractions by Receptor-Independent Enhancement of Calcium Sensitivity in Renal Arterioles Circ. Res., November 10, 2006; 99(10): 1117 - 1124. [Abstract] [Full Text] [PDF]