Sphingosine kinase 1
positive regulation of smooth muscle contraction
Sphingosine kinase modulates microvascular tone and myogenic responses through activation of RhoA/Rho kinase.
<h4>Background</h4>RhoA and Rho kinase are important modulators of microvascular tone.<h4>Methods and results</h4>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.<h4>Conclusions</h4>The tone-increasing effects of a Sphk1 overexpression suggest that Sphk1 may play an important role in the control of peripheral resistance.