Sphingosine kinase modulates microvascular tone and myogenic responses through activation of Rhoa/Rho kinase

Steffen Sebastian Bolz*, Lukas Vogel, Daniel Sollinger, Roland Derwand, Christa Boer, Stuart M. Pitson, Sarah Spiegel, Ulrich Pohl

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)342-347
Number of pages6
JournalCirculation
Volume108
Issue number3
DOIs
Publication statusPublished - 22 Jul 2003

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