Shear stress-dependent vasospasm induced by lysophosphatidic acid

我们以前已经表明，溶血磷脂酸（LPA），一种生物活性的血浆溶血磷脂，显着加速剪切应力。诱导培养的血管内皮细胞（EC）的Ca^2+反应。本研究旨在使用视频显微镜技术证明LPA和管腔切应力对离体大鼠肠系膜动脉（MA）血管调节的影响。虽然在0.03.0.3. M对MA基础张力无明显影响，在生理剪切条件下，LPA在相同浓度范围内可增加苯肾上腺素引起的MA收缩，减少乙酰胆碱引起的MA舒张。LPA的这种血管调节作用与管腔切应力水平呈正相关，可被LPA受体拮抗剂Ki 16425、环氧化酶抑制剂吲哚美辛和血栓素A_2受体拮抗剂SQ 29548所抑制。这些数据表明，LPA可以修改激动剂诱导的血管反应在MA在剪切应力。依赖的方式。LPA的这种作用是通过内皮细胞、LPA受体和环氧合酶/血栓素A_2信号通路介导的。

We have previously shown that lysophosphatidic acid(LPA), a bioactive plasma lysophospholipid, markedly accelerates shear stress. induced Ca^<2+> responses in cultured vascular endothelial cells(ECs). This study aimed to demonstrate the impact of LPA and luminal shear stress on vasomotor regulation in the isolated rat mesenteric artery(MA) using a videomicroscopic technique. Although the addition of LPA to the perfusate in a concentration range of 0.03.0.3. M had no significant effect on the basal MA tone, LPA in a similar concentration range led to increased phenylephrineinduced MA contraction and reduced acetylcholine-induced MA relaxation under physiological shear conditions. These vasomodulatory actions of LPA, which vanished upon removal of ECs, were positively dependent on luminal shear stress levels and were markedly inhibited by the LPA receptor antagonist Ki16425, the cyclooxygenase inhibitor indomethacin, and the thromboxane A_2 receptor antagonist SQ29548. These data thus suggest that LPA can modify the agonistinduced vasomotor responses in MAs in a shear stress. dependent manner. This effect of LPA was mediated through ECs, the LPA receptor, and cyclooxygenase/thromboxane A_2 signaling.