Attenuation by sphingosine-1-phosphate of rat microvessel acute permeability response to bradykinin is rapidly reversible

R. H. Adamson, R. K. Sarai, J. F. Clark, A. Altangerel, T. L. Thirkill, F. E. Curry

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

To evaluate the hypothesis that sphingosine-1-phosphate (S1P) and cAMP attenuate increased permeability of individually perfused mesenteric microvessels through a common Rac1-dependent pathway, we measured the attenuation of the peak hydraulic conductivity (L p) in response to the inflammatory agent bradykinin (BK) by either S1P or cAMP. We varied the extent of exposure to each agent (test) and measured the ratio L p test/L p BK alone for each vessel (anesthetized rats). S1P (1 μM) added at the same time as BK (concurrent, no pretreatment) was as effective to attenuate the response to BK (L p ratio: 0.14 ± 0.05; n = 5) as concurrent plus pretreatment with S1P for 30 min (L p ratio: 0.26 ± 0.06; n = 11). The same pretreatment with S1P, but with no concurrent S1P, caused no inhibition of the BK response (L p ratio 1.07 ± 0.11; n = 8). The rapid on and off action of S1P demonstrated by these results was in contrast to cAMP-dependent changes induced by rolipram and forskolin (RF), which developed more slowly, lasted longer, and resulted in partial inhibition when given either as pretreatment or concurrent with BK. In cultured endothelium, there was no Rac activation or peripheral cortactin localization at 1 min with RF, but cortactin localization and Rac activation were maximal at 1 min with S1P. When S1P was removed, Rac activation returned to control within 2 min. Because of such differing time courses, S1P and cAMP are unlikely to act through fully common effector mechanisms.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume302
Issue number10
DOIs
StatePublished - May 15 2012

Keywords

  • Adenosine 3',5'-cyclic monophosphate
  • Capillaries
  • Edema
  • Inflammation
  • Vascular permeability

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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