| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Research Abstract |
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.
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