This Article Full Text Full Text (PDF) All Versions of this Article: 41/4/891    most recent 01.HYP.0000058701.11991.C4v1 Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Eskildsen-Helmond, Y. E.G. Articles by Mulvany, M. J. Search for Related Content PubMed PubMed Citation Articles by Eskildsen-Helmond, Y. E.G. Articles by Mulvany, M. J. Related Collections Remodeling ACE/Angiotension receptors Cell signalling/signal transduction Hypertension - basic studies Smooth muscle proliferation and differentiation

(Hypertension. 2003;41:891.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Pressure-Induced Activation of Extracellular Signal-Regulated Kinase 1/2 in Small Arteries

From the Department of Pharmacology, University of Aarhus, Aarhus, Denmark.

Correspondence to Dr Y.E.G. Eskildsen-Helmond, Department of Pharmacology, University of Aarhus, University Park 240, DK-8000 Aarhus C, Denmark. E-mail ye{at}farm.au.dk

Extracellular signal-regulated kinase 1/2 (ERK1/2) may play a central signaling role in vascular remodeling. We investigated a possible combined role for the renin-angiotensin system and platelet-derived growth factor ß-receptor (PDGF-ß-R) in pressure-induced ERK1/2 activation in intact rat mesenteric small arteries. In an organ culture model, vessels were pressurized (70 mm Hg) for 1 hour plus a 5-minute intervention period. The intervention was either a rise in intraluminal pressure (up to 140 mm Hg) or challenge with angiotensin II (Ang II, 0.1 µmol/L) or PDGF-BB (30 µg/L). ERK1/2 activation was determined by Western blotting as formation of phosphorylated ERK1/2. All interventions caused ERK1/2 activation that was inhibited by the MEK inhibitor PD98059. The response to pressure was inhibited by an ACE inhibitor (perindoprilat), an Ang II receptor type 1 (R-AT₁) antagonist (candesartan), and tyrosine kinase inhibitors (genistein, herbimycin A). An R-AT₂ antagonist (PD123319) had no significant effect. Both a PDGF-receptor tyrosine kinase inhibitor (RPR101511A) and a neutralizing PDGF-ß-R antibody (AF385) inhibited the activation of ERK1/2 caused by PDGF-BB, Ang II, and pressure. That the latter interventions could indeed inhibit the PDGF-ß-R was supported by experiments with unmounted vessels in which PDGF-ß-R activation was measured by Western blot; both PDGF-BB and Ang II–mediated PDGF-ß-R activation were inhibited by RPR101511A and AF385. Immunohistochemistry showed that ERK1/2 and PDGF-ß-R was located in the adventitia, tunica media, and intima. The results suggest that pressure in rat mesenteric small arteries causes acute activation of ERK1/2 through pathways involving Ang II and PDGF-ß-R.

Key Words: platelet-derived growth factor • kinase • mesenteric arteries • rats • angiotensin-converting enzyme

This article has been cited by other articles:

				E. N.T.P. Bakker, C. L. Buus, J. A.E. Spaan, J. Perree, A. Ganga, T. M. Rolf, O. Sorop, L. H. Bramsen, M. J. Mulvany, and E. VanBavel Small Artery Remodeling Depends on Tissue-Type Transglutaminase Circ. Res., January 7, 2005; 96(1): 119 - 126. [Abstract] [Full Text] [PDF]

				E. C. Eringa, C. D. A. Stehouwer, G. P. van Nieuw Amerongen, L. Ouwehand, N. Westerhof, and P. Sipkema Vasoconstrictor effects of insulin in skeletal muscle arterioles are mediated by ERK1/2 activation in endothelium Am J Physiol Heart Circ Physiol, November 1, 2004; 287(5): H2043 - H2048. [Abstract] [Full Text] [PDF]

				F. Saez, C. Legare, J. Laflamme, and R. Sullivan Vasectomy-Dependent Dysregulation of a Local Renin-Angiotensin System in the Epididymis of the Cynomolgus Monkey (Macaca fascicularis) J Androl, September 1, 2004; 25(5): 784 - 796. [Abstract] [Full Text] [PDF]

				D. J. Kelly, A. J. Cox, R. M. Gow, Y. Zhang, B. E. Kemp, and R. E. Gilbert Platelet-Derived Growth Factor Receptor Transactivation Mediates the Trophic Effects of Angiotensin II In Vivo Hypertension, August 1, 2004; 44(2): 195 - 202. [Abstract] [Full Text] [PDF]