>Thank you for your summary of your interesting experiments. What mechanisms could be responsible for the apparent differences in the pathways used by steady and pulsatile stretches. Is it because genistein-sensitive pathways are downregulated by steady stretch, while herbimycin-sensitive pathways require time to be turned on?
Thank you for your question Dr Mulvany.
Apparently, herbimycin-sensitive pathways do not require much time to be activated, since as soon as five minutes after applying pressure to our vessels in organ culture, we found that the resulting MAP kinase activation depended on herbimycin-sensitive tyrosine kinases (Birukov et al, Circ Res 1997;81:895-903). Furthermore, both pulsatile and steady stretch experiments presented here were conducted during 24 hours, and unless it really takes much more time for pulsatile stretch to activate herbimycin-sensitive cascades, there is apparently no reason why this pathway would not be activated by 24 hours.
For the moment, we cannot rule out the possibility that genistein-sensitive pathways be downregulated by steady stretch (an appealing idea indeed), although we tend to favour - with support from our results obtained regarding FAK activation by steady but not pulsatile pressure - the hypothesis that in fact a completely different set of kinases is involved in sensing and tranducing steady versus pulsatile stretch. Of course, activation of one cascade does not rule out deactivation of a second, parallel pathway.