S1P (Sphingosine-1-Phosphate)-Induced Vasodilation in Human Resistance Arterioles During Health and Disease.
S1P (Sphingosine-1-Phosphate)-Induced Vasodilation in Human Resistance Arterioles During Health and Disease.
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DOI：
10.1161/hypertensionaha.122.19862
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发表时间：
2022-10
期刊：
影响因子：
8.3
通讯作者：
Freed, Julie K.
中科院分区：
文献类型：
--
作者：
Katunaric, Boran;SenthilKumar, Gopika;Schulz, Mary E.;De Oliveira, Nilto;Freed, Julie K.
临床前研究表明，1-磷酸鞘氨醇（S1 P）主要通过一氧化氮（NO）诱导的血管舒张作用影响血压调节。由于微血管张力显着有助于平均动脉压，S1 P对人体阻力小动脉的机制进行了研究。我们假设S1 P通过激活两种受体S1 PR 1和S1 PR 3诱导无冠状动脉疾病（nonCAD）的成人小动脉中NO介导的血管舒张。此外，我们测试了这种机制是否在被诊断患有冠状动脉疾病（CAD）的患者的血管中改变。从丢弃的手术脂肪组织中切下人小动脉（管腔直径为50-200 μm），插管并加压。平衡后，用内皮素-1（ET-1）预收缩阻力血管，并在存在或不存在各种抑制剂的情况下测量内径随S1 P浓度增加（10−12至10−7 M）的变化。S1 P导致显著的扩张，在用S1 PR 1和S1 PR 3抑制剂处理的血管中以及在每种受体表达降低的血管中被消除。在NOS抑制剂L-NAME和NO清除剂cPTIO的存在下，S1 P的扩张显著减少。有趣的是，在PEG-过氧化氢酶、夹竹桃黄素和NADPH氧化酶（NOX）2和4的特异性抑制剂的存在下，扩张也显著受损。来自被诊断患有冠状动脉疾病（CAD）的患者的血管中的扩张仅依赖于H2 O2，而H2 O2仅依赖于S1 PR 3激活。这些翻译研究突出了在血管信号传导中观察到的种间差异，并提供了对S1 P调节微血管阻力和最终调节人类血压的机制的深入了解。
Preclinical studies suggest that sphingosine-1-phophate (S1P) influences blood pressure regulation primarily through nitric-oxide (NO)-induced vasodilation. Since microvascular tone significantly contributes to mean arterial pressure, the mechanism of S1P on human resistance arterioles was investigated. We hypothesized that S1P induces NO-mediated vasodilation in human arterioles from adults without coronary artery disease (nonCAD) through activation of two receptors, S1PR1 and S1PR3. Further, we tested whether this mechanism is altered in vessels from patients diagnosed with coronary artery disease (CAD). Human arterioles (50-200 μm in luminal diameter) were dissected from otherwise discarded surgical adipose tissue, cannulated, and pressurized. Following equilibration, resistance vessels were pre-constricted with endothelin-1 (ET-1) and changes in internal diameter to increasing concentrations of S1P (10−12 to 10−7 M) in the presence or absence of various inhibitors were measured. S1P resulted in significant dilation that was abolished in vessels treated with S1PR1 and S1PR3 inhibitors and in vessels with reduced expression of each receptor. Dilation to S1P was significantly reduced in the presence of the NOS inhibitor L-NAME and the NO scavenger cPTIO. Interestingly, dilation was also significantly impaired in the presence of PEG-catalase, apocynin, and specific inhibitors of NADPH oxidases (NOX) 2 and 4. Dilation in vessels from patients diagnosed with coronary artery disease (CAD) was dependent on H2O2 alone which was only dependent on S1PR3 activation. These translational studies highlight the inter-species variation observed in vascular signaling and provide insight into the mechanism by which S1P regulates microvascular resistance and ultimately blood pressure in humans.
影响因子：
7.4
作者：
Tian, Jing;Hou, Yali;Lu, Qing;Wiseman, Dean A.;Fonsesca, Fabio Vasconcelos;Elms, Shawn;Fulton, David J.;Black, Stephen M.
通讯作者：
Black, Stephen M.