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

Bolz S.S., Vogel L., Sollinger D., Derwand R., Boer C., Pitson S.M., Spiegel S., Pohl U.

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.

Circulation 108:342-347(2003) [PubMed] [Europe PMC]

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