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Bolz, S.S. et al.

Bolz, Vogel, Sollinger, Derwand, Boer, Pitson, Spiegel, Pohl,

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

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.[1]

References

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. Circulation (2003) [Pubmed]

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