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 language | English |
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Pages (from-to) | 342-347 |
Number of pages | 6 |
Journal | Circulation |
Volume | 108 |
Issue number | 3 |
DOIs | |
Publication status | Published - 22 Jul 2003 |
Keywords
- Arteries
- Genetics
- Microcirculation
- Muscle, smooth
- Vasoconstriction