Invited Symposium: Hypertension I: Structure of Small Arteries in Hypertension



Materials & Methods


Discussion & Conclusion



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Differential Signal Transduction of Pulsatile and Static Stretch in the Vessel Wall.

Lehoux, S (INSERM U141, Hopital Lariboisiere, Paris, France)
Tedgui, A (INSERM U141, Hopital Lariboisiere, Paris, France)

Contact Person: Stephanie Lehoux (slehoux@mailcity.com)


The vessel wall is under constant mechanical stress due to blood pressure and to pulsatile blood flow. Steady and cyclic stretch have both been shown to modulate smooth muscle cell morphology and function. Activation of the mitogen-activated protein kinase (MAPK) cascade is likely to account for at least part of the changes in protein synthesis and gene expression observed. Nevertheless, some responses to mechanical stress are likely to be transmitted via extracellular matrix components which are incomplete in most in vitro studies. We therefore used an organ model of rabbit aorta, cannulated and perfused 24 hours with DMEM+20% FCS, to verify effects of steady and cyclic stretch on MAPK activity. Applying a steady pressure of 150 mmHg produced an important rise in MAPK activity compared to control vessels kept at 50 mmHg. This increase was blocked by herbimycin A, a Src-family tyrosine kinase inhibitor, but not by other tyrosine kinase inhibitors. On the other hand, submitting aortas to a pulsatile 10% variation in vessel diameter produced a lesser increase in MAPK activity, which was inhibited at least in part by tyrosine kinase inhibitors genisteine and tyrphostin A48 but not by herbimycin A. Furthermore, only a steady stretch of vessel segments led to an increase in phosphorylation of focal adhesion kinase (FAK). It therefore appears that pulsatile and steady stretch of vessels activate MAPK activity via distinct pathways.

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Presentation Number SAlehoux0704
Keywords: MAP kinase, Tyrosine kinase, Src, focal adhesion

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Lehoux, S; Tedgui, A; (1998). Differential Signal Transduction of Pulsatile and Static Stretch in the Vessel Wall.. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/mulvany/lehoux0704/index.html
© 1998 Author(s) Hold Copyright