Preoperative administration of both FTY720 and Decoquinate SEW2871 normalized the vascular reactivity by increasing the vascular responsiveness to PE and SE. In contrast, the vascular relaxation to ACh was essentially unchanged in Sham and CPB during 5 days of recovery. However, both FTY720 and SEW2871 increased ACh induced vascular relaxation in both vascular beds by about 20�C25%. Thus, both compounds evoked hypotension, improved vascular contractile and relaxant responsiveness, yet differentially decreased the amount of lymphocytes in the peripheral blood. These data suggest that the observed systemic vascular treatment effects of FTY720 and SEW2871 were independent from lymphopenia but rather involved the modulation of vascular S1P1 receptors. Vascular PJ34 hydrochloride dysfunction contributes to multiple organ dysfunction syndrome after CPB and is therefore considered to be a relevant target of therapy. We found that contractility of both mesenteric and coronary arteries was impaired by both experimental procedures, most prominently at one day of recovery. The finding that both Sham and CPB negatively affects the vascular contractile function, suggests that the minor surgical procedures and/or extended anesthesia induce these extensive and protracted changes in the contractility of small vessels, rather than ECC. In addition, we found that the relaxant vascular function was much less affected: only the relaxant function of mesenteric arteries was briefly affected following CPB and only minor effects of surgery were found on the relaxant function of the coronary arteries. Collectively, our data suggest that anesthesia and cannulation have a long-lasting impact on the vasoresponsiveness of small arteries, which warrants further investigation into its mechanism and the contribution of different types of anesthetics. Although S1P is of importance in the entire human body, it is a major regulator of the vascular and immune system. In this respect, the immunomodulatory effects of S1P agonists have been associated with the inhibition after S1P receptor activation of the egress of lymphocytes from secondary lymphoid organs to peripheral blood.