Taken together, both FTY720 and SEW2871 similarly decreased the blood pressure during surgery, which suggests it is mediated mainly by S1P1 receptor mediated signaling. The depressed mesenteric Palonosetron hydrochloride contractility was used to evaluate the potential of agonists of S1P receptors to modulate Azelnidipine vascular dysfunction in CPB. We show that injection of a S1P1 receptor agonist improves the vascular contractile and relaxant function of mesenteric and coronary arteries and thereby, at least in part, preclude the negative effects of surgery and CPB on these vessels. Despite the differential effects of FTY720 and SEW2871 on circulating lymphocytes in the present study, both compounds shared a similar effect on vascular reactivity and blood pressure, which suggests that the effects on the vascular function occur independently of immunological changes, but rather involve modulation of vascular S1P receptors. The comparable effect of both FTY720 and SEW2871 on vascular contractility suggests the involvement of S1P1 receptor dependent mechanism, whereas vascular smooth muscle were reported to express mainly S1P2 and S1P3 receptors that mediate vasoconstriction through activation of the phospholipase C, myosin light chain kinase and/or Rho-associated kinase dependent inhibition of myosin light chain phosphatase. However, other studies found the involvement of S1P1 receptors in the regulation of contractile reactivity and S1P agonist were found recently to evoke vasoconstriction of the afferent renal arterioles via S1P1 and S1P2 receptors with involvement of the L type voltage-dependent calcium channels. Further, S1P induces COX-2 expression in vascular smooth muscle cells, which seems partially mediated via S1P1 receptors. Thus, S1P1 receptor may be more prominently involved in VSMC regulation than reported so far. Alternatively, the similar effect of FTY720 and SEW2871 on VSM contractility may be dependent on S1P receptors expressed on the endothelium. Indeed, FTY720 evokes endothelium dependent VSMC contraction most likely via COX/ thromboxane A2 route and sphingosine kinase.