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Published on: September 12, 2015
Sphingosine kinase modulates microvascular tone and myogenic responses through activation of RhoA/Rho kinase
Steffen-Sebastian Bolz1, Lukas Vogel, Daniel Sollinger
1Institute of Physiology, Ludwig Maximilians University, Schillerstrasse 44, 80336 Muenchen, Germany. bolz@lrz.uni-muenchen.de
Background:
RhoA and Rho kinase are important modulators of microvascular tone.
Methods And Results:
We tested whether sphingosine kinase (Sphk1) that generates the endogenous sphingolipid mediator sphingosine-1-phosphate (S1P) is part of a signaling cascade to activate the RhoA/Rho kinase pathway. Using a new transfection model, we report that resting tone and myogenic responses of isolated resistance arteries increased with forced expression of Sphk1 in smooth muscle cells of these arteries. Overexpression of a dominant negative Sphk1 mutant or coexpression of dominant negative mutants of RhoA or Rho kinase together with Sphk1 completely inhibited development of tone and myogenic responses.
Conclusions:
The tone-increasing effects of a Sphk1 overexpression suggest that Sphk1 may play an important role in the control of peripheral resistance.
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