Sphingosine‐1‐phosphate reduces rat renal and mesenteric blood flow <i>in vivo</i> in a pertussis toxin‐sensitive manner

Bischoff, Angela; Czyborra, Peter; Heringdorf, Dagmar Meyer zu; Jakobs, Karl H.; Michel, Martin C.

doi:10.1038/sj.bjp.0703516

Cited by 80 publications

(71 citation statements)

References 24 publications

(41 reference statements)

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“…To further support our in vitro findings, we performed an in vivo study by measuring RBF responses to bolus injections of S1P in anesthetized rats. Consistent with the report by Bischoff et al, 15 intravenous injection of exogenous S1P decreased RBF without significant changes in BP. The rapid reduction and recovery in RBF in response to a bolus of S1P are consistent with the behavior of S1P on afferent arteriolar reactivity measured in the in vitro.…”

Section: Discussionsupporting

confidence: 82%

“…1,2,5 Recent studies indicate that S1P plays an important role in regulating vascular tone in resistance vessels, including cerebral, coronary, and mesenteric arteries 16,[27][28][29][30][31][32] ; however, very little is known about the renal influence of S1P under either physiologic or pathophysiologic conditions. Bischoff et al reported that S1P vasoconstricted isolated intrarenal arteries 14 and reduced RBF without changing arterial pressure in anesthetized rats, 15 indicating that S1P may be an important regulator of renal vascular function. The intrarenal arteries, however, contribute less to overall renal vascular resistance than microvessels and the S1P receptor signaling pathways involved in S1P-mediated renal vasoconstriction are also unknown.…”

Section: Discussionmentioning

confidence: 99%

“…14 Intravenous infusion of S1P to rats in vivo decreased renal blood flow (RBF) without changing mean arterial pressure. 15 Genetic studies found a significantly higher RBF in anesthetized S1P2 gene knockout mice compared with wild-type mice. 16 These studies suggest that S1P may be important in regulating renal vascular function.…”

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confidence: 99%

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Sphingosine-1-Phosphate Evokes Unique Segment-Specific Vasoconstriction of the Renal Microvasculature

Guan¹,

Singletary²,

Cook³

et al. 2014

Journal of the American Society of Nephrology

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Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, has been implicated in regulating vascular tone and participating in chronic and acute kidney injury. However, little is known about the role of S1P in the renal microcirculation. Here, we directly assessed the vasoresponsiveness of preglomerular and postglomerular microvascular segments to exogenous S1P using the in vitro blood-perfused juxtamedullary nephron preparation. Superfusion of S1P (0.001-10 mM) evoked concentration-dependent vasoconstriction in preglomerular microvessels, predominantly afferent arterioles. After administration of 10 mM S1P, the diameter of afferent arterioles decreased to 35%65% of the control diameter, whereas the diameters of interlobular and arcuate arteries declined to 50%612% and 68%66% of the control diameter, respectively. Notably, efferent arterioles did not respond to S1P. The S1P receptor agonists FTY720 and FTY720-phosphate and the specific S1P1 receptor agonist SEW2871 each evoked modest afferent arteriolar vasoconstriction. Conversely, S1P2 receptor inhibition with JTE-013 significantly attenuated S1P-mediated afferent arteriolar vasoconstriction. Moreover, blockade of L-type voltage-dependent calcium channels with diltiazem or nifedipine attenuated S1P-mediated vasoconstriction. Intravenous injection of S1P in anesthetized rats reduced renal blood flow dose dependently. Western blotting and immunofluorescence revealed S1P1 and S1P2 receptor expression in isolated preglomerular microvessels and microvascular smooth muscle cells. These data demonstrate that S1P evokes segmentally distinct preglomerular vasoconstriction via activation of S1P1 and/or S1P2 receptors, partially via L-type voltagedependent calcium channels. Accordingly, S1P may have a novel function in regulating afferent arteriolar resistance under physiologic conditions. 25: 177425: -178525: , 201425: . doi: 10.1681 Sphingosine 1-phosphate (S1P) is recognized as an important signaling molecule in diverse biologic processes. 1,2 Growing evidence indicates that S1P plays an important role in regulating vascular reactivity. 3-5 S1P is a bioactive sphingolipid metabolite and is released from erythrocytes, platelets, and endothelial cells. 6,7 The majority of S1P effects are mediated via five distinct receptors (S1P1-S1P5 receptors), which represent a family of small G proteincoupled receptors (GPCRs) 5 ; however, S1P can also exist in the cytoplasm as a second messenger involved in Ca 2+ mobilization or cell survival and proliferation. 8,9 S1P1-S1P3 receptors are expressed by a wide variety of tissues, whereas S1P4 and S1P5 receptors are mainly expressed in cells of the immune and nervous systems. 4,10 In the vasculature, endothelial cells mainly express S1P1 and S1P3 with variable expression of S1P2, whereas vascular smooth muscle cells express S1P2 and S1P3 with variable expression of S1P1. [3][4][5] Studies in animals show that application of exogenous S1P J Am Soc Nephrol

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

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Sphingosine-1-Phosphate Evokes Unique Segment-Specific Vasoconstriction of the Renal Microvasculature

Guan¹,

Singletary²,

Cook³

et al. 2014

Journal of the American Society of Nephrology

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“…In addition, our results suggest that the mechanism by which this facilitatory response occurs is associated with change of S1P 3 expression during culture. S1P caused slight vasoconstriction in rat renal and mesenteric micro-vessels (26). In addition, S1P did not induce any contractile response in coronary, femoral, and carotid arteries isolated from rats (21).…”

Section: Discussionmentioning

confidence: 94%

Cell-Culture–Dependent Change of Ca2+ Response of Rat Aortic Myocytes to Sphingosine-1-Phosphate

et al. 2008

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Abstract. We characterized the effects of sphingosine-1-phosphate (S1P) on rat aortic myocytes with or without culture. Application of S1P induced a small Ca 2+ response in 40% freshly dispersed aortic myocytes, whereas S1P caused a larger Ca 2+ response in 90% myocytes cultured for 72 h. Concentration-response relationships of S1P in cultured myocytes were significantly different from that in non-cultured myocytes. Analysis of the expression of S1P-receptor mRNA transcripts revealed that S1P-receptor type 3 (S1P 3 ) was significantly increased when myocytes were cultured for 24 h. Neither the removal of serum from culture medium nor pretreatment with pharmacological agents, such as ERK, Rho, and PI3 kinase inhibitors, affected the progression of the S1P-induced Ca 2+ response during culture. The sustained component of the Ca 2+ response to S1P was sensitive to the removal of external Ca 2+ and was effectively inhibited by inorganic Ca 2+ -channel blockers such as Gd 3+, Cd 2+ , and Ni 2+. However, application of S1P did not induce any contraction in organ-cultured as well as the intact aorta muscle strip. Aortic myocytes freshly dispersed from the organ-cultured muscle were also ineffective against S1P. Taken together, cell-culture changes the S1P 3 -mediated Ca 2+ response to S1P in rat aortic myocytes.

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“…S1P receptor expression has been documented in endothelial as well as in vascular smooth muscle cells 19,23 . Bischoff et al 24,25 indeed reported that S1P constricted renal and mesenteric microvessels in vitro and reduced renal and mesenteric blood flow in vivo. As yet, however, there is no study to explore the expression and role of S1P expression in the cerebral vasospasm after SAH.…”

Section: Introductionmentioning

confidence: 99%

Expression of Sphingosine-1-phosphate (S1P) on the cerebral vasospasm after subarachnoid hemorrhage in rabbits

et al. 2015

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PURPOSE: To demonstrate the relationship between of sphingosine-1-phosphate (S1P) expression and subarachnoid hemorrhage (SAH). METHODS:The basilar arteries from a "double-hemorrhage" rabbit model of SAH were used to investigate the relation between S1P expression and SAH. Various symptoms, including blood clots, basilar artery cross-sectional area, and S1P phosphatase expression were measured at day 3, 5, 7, 9. RESULTS:The expression of S1P was enhanced in the cerebral vasospasm after subarachnoid hemorrhage in the rabbits. And S1P expression was consistent with the basilar artery cross-sectional area changes at day 3, 5, 7, 9.CONCLUSION: Sphingosine-1-phosphate expression in the cerebral arterial may be a new indicator in the development of cerebral vasospasm after subarachnoid hemorrhage and provide a new therapeutic method for SAH.

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Sphingosine‐1‐phosphate reduces rat renal and mesenteric blood flow in vivo in a pertussis toxin‐sensitive manner

Cited by 80 publications

References 24 publications

Sphingosine-1-Phosphate Evokes Unique Segment-Specific Vasoconstriction of the Renal Microvasculature

Sphingosine-1-Phosphate Evokes Unique Segment-Specific Vasoconstriction of the Renal Microvasculature

Cell-Culture–Dependent Change of Ca2+ Response of Rat Aortic Myocytes to Sphingosine-1-Phosphate

Expression of Sphingosine-1-phosphate (S1P) on the cerebral vasospasm after subarachnoid hemorrhage in rabbits

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