gms | German Medical Science

28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

24. bis 27.11.2004, Hannover

S1P3-receptor may play a role in blood pressure regulation and control of endothelial function

Der S1P3-Rezeptor spielt möglicherweise bei der Blutdruckregulation und Steuerung der Endothelfunktion eine Rolle

Meeting Abstract (Hypertonie 2004)

Suche in Medline nach

  • M. Tölle - Med. Klinik IV - Charité, Campus Benjamin Franklin (Berlin, D)
  • W. Zidek - Med. Klinik IV - Charité, Campus Benjamin Franklin (Berlin, D)
  • M. van der Giet - Med. Klinik IV - Charité, Campus Benjamin Franklin (Berlin, D)

Hypertonie 2004. 28. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Hannover, 24.-27.11.2004. Düsseldorf, Köln: German Medical Science; 2005. Doc04hochP115

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2004/04hoch115.shtml

Veröffentlicht: 10. August 2005

© 2005 Tölle et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Recently we could demonstrate that HDL can directly affect blood pressure. Until now it is speculated that sphingolipids which are components of HDL might affect vascular tone regulation. We could already show that various sphingolipids like sphingosylphosphorylcholine and lysosulfatidic acid are able to activate eNOS. In the present study we investigated a further sphingolipid which is component of HDL: sphingosine-1-phosphate (S1P). We wanted to demonstrate that this substance can affect blood pressure and elucidate the corresponding signaltransduction pathway.

Arterial relaxations studies were done in phenylephrine (PE 1µmol/L) precontracted aortae from wildtype mice, eNOS knockout mice and S1P-receptor type 3 knockout mice using a wire myograph. Detection of intracellular NO generation in HUVEC was done using the NO-sensitive fluorescence dye DAF-2DA analyzing by a fluorescence microscopy. Activation of eNOS was measured by Western blotting using anti-phospho-eNOS antibodies.

Application S1P induced a potent dose-dependent vasorelaxation in PE-precontracted aortae from wild-type mice (EC50: 7.6±0.4). Application of 10 µmol/L S1P to PE-precontracted aortae from wildtype mice induced maximum vasodilation. The maximal S1P-induced vasodilation was about 30% of the maximal vasodilation induced by acetylcholine (10 mmol/L). S1P did not show any vasorelaxation in PE-precontracted arotae form eNOS knockout mice and EDG3-receptor knockout mice. Stimulation of HUVEC with S1P (1 µmol/L) induced intracellular NO generation using NO-sensitive fluorescence dye DAF-2DA. Stimulation of HUVEC with S1P induced a significant increase in phosphorylation of eNOS-protein.

S1P is a potent endothelium-dependent vasorelaxing sphingolipid activating S1P-3-receptors. Activation of S1P-3-receptor might ameliorate endothelial function. S1P might therefore play a role in vascular tone control and pathogenesis of hypertension and endothelial dysfunction.