AJP - Heart Calcium Transients and Cell-Sarcomere
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 284: H2045-H2052, 2003; doi:10.1152/ajpheart.01089.2002
0363-6135/03 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (12)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Dantas, A. P. V.
Right arrow Articles by Michel, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Dantas, A. P. V.
Right arrow Articles by Michel, T.
Vol. 284, Issue 6, H2045-H2052, June 2003

Sphingosine 1-phosphate and control of vascular tone

Ana Paula V. Dantas1, Junsuke Igarashi1,3, and Thomas Michel1,2

1 Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston 02115; 2 Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts 02132; and 3 Second Department of Physiology, Kagawa Medical School, Kagawa, 761-0793 Japan

Sphingosine-1-phosphate (S1P) is a platelet-derived lipid mediator that activates the endothelial isoform of nitric oxide synthase (eNOS) in endothelial cells. However, the role of S1P in endothelium-dependent vasodilation and the signaling pathways elicited by S1P in intact vessels are largely unknown. We found that S1P induces dose-dependent transient relaxation of isolated pressurized mesenteric arterioles (EC50 10 ± 3 nM); maximal vasodilation (55 ± 8%) is seen ~2 min after S1P addition and returns to baseline by 5 min. S1P promotes comparable responses in arterioles from wild-type but not eNOSnull mice. S1P-induced vasodilation is abrogated by removal of endothelium or by the addition of the NOS inhibitor Nomega -monomethyl-L-arginine but is not affected by the cyclooxygenase inhibitor indomethacin, nor by the blockade of K+ channels by using 4-aminopyridine. S1P-induced vasodilation is attenuated by pertussis toxin, by the phosphoinositide 3-kinase (PI3-kinase) inhibitor wortmannin, and by the calcium chelator BAPTA. With the use of high-sensitivity protein immunoblots in extracts from single pressurized vessels, we found that S1P, but not bradykinin, promotes the phosphorylation of eNOS at Ser1179. Maximum S1P-induced eNOS Ser1179 phosphorylation was reached at the time of maximum vasorelaxation, but enzyme phosphorylation persisted for several minutes after vasodilation had resolved. Thus regulatory pathways distinct from eNOS Ser1179 dephosphorylation serve to terminate agonist-promoted vasorelaxation. Taken together, our findings demonstrate that S1P, an important intercellular mediator of platelet-vessel wall interactions, is a effective arteriolar vasodilator that acts via G protein-dependent, calcium-sensitive, and PI3-kinase-modulated signaling pathways.

sphingolipids; endothelium-dependent relaxation; nitric oxide; endothelial nitric oxide synthase phosphorylation.


This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
S.-K. Choi, D.-S. Ahn, and Y.-H. Lee
Comparison of contractile mechanisms of sphingosylphosphorylcholine and sphingosine-1-phosphate in rabbit coronary artery
Cardiovasc Res, May 1, 2009; 82(2): 324 - 332.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
J. Igarashi and T. Michel
Sphingosine-1-phosphate and modulation of vascular tone
Cardiovasc Res, May 1, 2009; 82(2): 212 - 220.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
K. Omori, Y. Shikata, K. Sarai, N. Watanabe, J. Wada, N. Goda, N. Kataoka, K. Shikata, and H. Makino
Edaravone mimics sphingosine-1-phosphate-induced endothelial barrier enhancement in human microvascular endothelial cells
Am J Physiol Cell Physiol, November 1, 2007; 293(5): C1523 - C1531.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
J. Igarashi, M. Miyoshi, T. Hashimoto, Y. Kubota, and H. Kosaka
Hydrogen peroxide induces S1P1 receptors and sensitizes vascular endothelial cells to sphingosine 1-phosphate, a platelet-derived lipid mediator
Am J Physiol Cell Physiol, February 1, 2007; 292(2): C740 - C748.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
J. N. Lorenz, L. J. Arend, R. Robitz, R. J. Paul, and A. J. MacLennan
Vascular dysfunction in S1P2 sphingosine 1-phosphate receptor knockout mice
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R440 - R446.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
K. G. Soucy, S. Ryoo, A. Benjo, H. K. Lim, G. Gupta, J. S. Sohi, J. Elser, M. A. Aon, D. Nyhan, A. A. Shoukas, et al.
Impaired shear stress-induced nitric oxide production through decreased NOS phosphorylation contributes to age-related vascular stiffness
J Appl Physiol, December 1, 2006; 101(6): 1751 - 1759.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
D. G. Hemmings, N. K. Hudson, D. Halliday, M. O'Hara, P. N. Baker, S. T. Davidge, and M. J. Taggart
Sphingosine-1-Phosphate Acts via Rho-Associated Kinase and Nitric Oxide to Regulate Human Placental Vascular Tone
Biol Reprod, January 1, 2006; 74(1): 88 - 94.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
S.-H. Hsiao, P. D. Constable, G. W. Smith, and W. M. Haschek
Effects of Exogenous Sphinganine, Sphingosine, and Sphingosine-1-Phosphate on Relaxation and Contraction of Porcine Thoracic Aortic and Pulmonary Arterial Rings
Toxicol. Sci., July 1, 2005; 86(1): 194 - 199.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
D. T. Bolick, S. Srinivasan, K. W. Kim, M. E. Hatley, J. J. Clemens, A. Whetzel, N. Ferger, T. L. Macdonald, M. D. Davis, P. S. Tsao, et al.
Sphingosine-1-Phosphate Prevents Tumor Necrosis Factor-{alpha}-Mediated Monocyte Adhesion to Aortic Endothelium in Mice
Arterioscler. Thromb. Vasc. Biol., May 1, 2005; 25(5): 976 - 981.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
M. Tolle, B. Levkau, P. Keul, V. Brinkmann, G. Giebing, G. Schonfelder, M. Schafers, K. v. W. Lipinski, J. Jankowski, V. Jankowski, et al.
Immunomodulator FTY720 Induces eNOS-Dependent Arterial Vasodilatation via the Lysophospholipid Receptor S1P3
Circ. Res., April 29, 2005; 96(8): 913 - 920.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
R. Bhatia, K. Matsushita, M. Yamakuchi, C. N. Morrell, W. Cao, and C. J. Lowenstein
Ceramide Triggers Weibel-Palade Body Exocytosis
Circ. Res., August 6, 2004; 95(3): 319 - 324.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. Forrest, S.-Y. Sun, R. Hajdu, J. Bergstrom, D. Card, G. Doherty, J. Hale, C. Keohane, C. Meyers, J. Milligan, et al.
Immune Cell Regulation and Cardiovascular Effects of Sphingosine 1-Phosphate Receptor Agonists in Rodents Are Mediated via Distinct Receptor Subtypes
J. Pharmacol. Exp. Ther., May 1, 2004; 309(2): 758 - 768.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
J. D. Saba and T. Hla
Point-Counterpoint of Sphingosine 1-Phosphate Metabolism
Circ. Res., April 2, 2004; 94(6): 724 - 734.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2003 by the American Physiological Society.