Sphingosine‐1‐phosphate induced vasoconstrictor responses decreased in cerebral arteries of endotoxemic rats

Abstract

IntroductionSepsis is the leading cause of mortality in intensive care units. Vascular dysfunction is the most important cause of death in sepsis. There are some data in the literature for vascular hyporesponsiveness to miscellaneous vasopressors. However most of the data are about resistance mesenteric artery and aorta which is the biggest artery in the body. The responses of cerebral arteries to vasopressors were not investigated in vitro while the brain blood flows were investigated in sepsis.Sphingosine‐1‐phosphate (S1P) is a bioactive lipid mediator which has several physiological functions in cell growth, inflammation, endothelial barrier integrity and vascular tone. Serum S1P levels decrease in sepsis and this decrement is correlated with the severity of sepsis. S1P is a vasoconstrictor lipid mediator which has more vasoconstrictor responses in small sized vessels and brain arteries. Our aim is to study the vasoconstrictor responses of the brain and mesenteric arteries to S1P in sepsis.Material and Methods10 mg/kg lipopolysaccharide (serotype O55:B5) were given intraperitoneally to rats to make an animal model os sepsis. Rats were anesthetized with gaseous carbon dioxide and decapitated 20 hours after injection, Basilar, anterior cerebral, middle cerebral and 3rd branch of mesenteric arteries were mounted in a wire myograph. Arteries were stimulated with 124 nM K+‐PSS after 30 min stabilization. Concentration‐response curves for S1P were evaluated.ResultsHigh K+ responses did not change in brain and peripheral arteries. S1P‐induced vasoconstrictor responses decreased in anterior and prominently in middle cerebral arteries. S1P‐induced vasoconstrictor responses in basilar and mesenteric arteries did not change.ConclusionsThis is the first study that show the alterations of S1P‐induced vasoconstrictor responses of brain arteries in sepsis. The difference in the alteration of S1P responses of cerebral arteries may explain the alteration and redistribution of cerebral perfussion in sepsis.Support or Funding InformationThis study was funded by Hacettepe University Scientific Research Projects Coordination Unit (TSA‐2017‐12848).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.