Department of Pharmacology and Internal Medicine, and Center for Lung Biology, University of South Alabama College of Medicine, Mobile, Alabama, USA.
Pulm Circ. 2011 Jul-Sep;1(3):399-404. doi: 10.4103/2045-8932.87309.
This study aimed to identify receptors mediating sphingosine-1-phosphate (S1P)-induced vasoconstriction in the normotensive and chronic hypoxia-induced hypertensive rat pulmonary circulation. In isolated perfused lungs from normoxic rats, infusion of S1P caused a sustained vasoconstriction, which was not reduced by combinational pretreatment with the dual S1P(1 and 3) receptor antagonist VPC23019 and the S1P(2) receptor antagonist JTE013. The S1P(4) receptor agonists phytosphingosine-1-phospate and VPC23153, but not the dual S1P(1 and 3) receptor agonist VPC24191, caused dose-dependent vasoconstrictions. In hypertensive lungs from chronically hypoxic rats, the vasoconstrictor responses to S1P and VPC23153 were markedly enhanced. The S1P(4) receptor agonist VPC 23153 caused contraction of isolated pulmonary but not of renal or mesenteric arteries from chronically hypoxic rats. S1P(4) receptor protein as well as mRNA were detected in both normotensive and hypertensive pulmonary arteries. In contrast to what has been reported in the systemic circulation and mouse lung, our findings raise the possibility that S1P(4) receptor plays a significant role in S1P-induced vasoconstriction in the normotensive and hypertensive rat pulmonary circulation.
本研究旨在鉴定介导鞘氨醇-1-磷酸（S1P）诱导的正常血压和慢性低氧诱导的高血压大鼠肺循环血管收缩的受体。在来自正常氧合大鼠的离体灌注肺中，S1P 的输注引起持续的血管收缩，联合预处理双重 S1P（1 和 3）受体拮抗剂 VPC23019 和 S1P（2）受体拮抗剂 JTE013 并不能减轻这种收缩。S1P（4）受体激动剂植物鞘氨醇-1-磷酸和 VPC23153 引起剂量依赖性的血管收缩，但双重 S1P（1 和 3）受体激动剂 VPC24191 则没有。在慢性低氧大鼠的高血压肺中，S1P 和 VPC23153 的血管收缩反应明显增强。S1P（4）受体激动剂 VPC 23153 引起慢性低氧大鼠离体肺血管收缩，但对肾或肠系膜动脉没有收缩作用。S1P（4）受体蛋白和 mRNA 均在正常血压和高血压肺血管中检测到。与在体循环和小鼠肺中报道的情况相反，我们的研究结果表明，S1P（4）受体在正常血压和高血压大鼠肺循环中 S1P 诱导的血管收缩中可能发挥重要作用。
