on July 7, 2003
Published online before print July 7, 2003, doi: 10.1161/01.CIR.0000080324.12530.0D
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Submitted on February 19, 2003
From the Institute of Physiology, Ludwig-Maximilians-University, Munich, Germany (S.-S.B., L.V., D.S., R.D., U.P.); the Institute for Cardiovascular Research, Vrije Universiteit Medical Center, Amsterdam, the Netherlands (C.B.); the Hanson Institute, Human Immunology, Institute of Medical and Veterinary Science, Adelaide, Australia (S.M.P.); and the Department of Biochemistry, Medical College of Virginia, Virginia Commonwealth University, Richmond (S.S.). * To whom correspondence should be addressed. E-mail: bolz{at}lrz.uni-muenchen.de.
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.
Revised on April 2, 2003
Accepted on April 4, 2003
Sphingosine Kinase Modulates Microvascular Tone and Myogenic Responses Through Activation of RhoA/Rho Kinase
Steffen-Sebastian Bolz MD*,
Key words: microcirculation • muscle, smooth • arteries • genetics • vasoconstriction
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