Yang B C, Chandna V K, Lawson D L, Mehta J L
Department of Medicine, University of Florida College of Medicine, Gainesville.
J Cardiovasc Pharmacol. 1993 Feb;21(2):249-55. doi: 10.1097/00005344-199302000-00010.
Previous studies indicate that anoxia results in vascular smooth muscle contraction, and this phenomenon is mediated in part by a decrease in release of endothelium-derived relaxing factor (EDRF). The role of platelets that relax blood vessels by eliciting EDRF release on anoxic contraction is not known. To examine anoxic contraction in the presence of platelets, we exposed norepinephrine (NE)-precontracted rat aortic rings to washed platelets and then induced anoxia (switch from 95% O2 to 95% N2). Platelets transiently relaxed the precontracted aortic rings (decrease in tension 49 +/- 4%, n = 18). The subsequent anoxia-induced contraction was augmented, however (magnitude of contraction 71 +/- 12 vs. 49 +/- 6% in parallel buffer-treated rings, n = 18, p < 0.01). To determine the mechanism of platelet-mediated augmentation of anoxic contraction, vascular rings were treated with indomethacin, the thromboxane A2 (TxA2)/endoperoxide receptor antagonist SQ29,548, lipoxygenase inhibitor U60,257B, free oxygen radical scavengers superoxide dismutase (SOD) plus catalase, serotonin (S2) receptor blocker LY53,857, or the ADP scavenger apyrase. Although apyrase, U60,257B, SQ29,548, LY53,857, and SOD plus catalase had no effect on augmentation of anoxic contraction in the presence of platelets, treatment with indomethacin markedly decreased (p < 0.02) the augmented anoxic vasoconstriction. Because indomethacin decreases the activity of platelet-activating factor (PAF), vascular rings were treated with two different specific PAF receptor antagonists: L-659,989 and WEB 2170 BS. Both these agents blocked the platelet-augmented anoxic vasoconstriction. In addition, synthetic PAF (10(-7) and 10(-6) M) in itself potentiated anoxic contraction, mimicking the activity of platelets.(ABSTRACT TRUNCATED AT 250 WORDS)
以往研究表明，缺氧会导致血管平滑肌收缩，且这种现象部分是由内皮源性舒张因子（EDRF）释放减少介导的。血小板通过在缺氧收缩时引发EDRF释放来舒张血管，其作用尚不清楚。为了研究血小板存在时的缺氧收缩情况，我们将去甲肾上腺素（NE）预收缩的大鼠主动脉环暴露于洗涤过的血小板中，然后诱导缺氧（从95% O₂切换至95% N₂）。血小板使预收缩的主动脉环短暂舒张（张力降低49±4%，n = 18）。然而，随后缺氧诱导的收缩增强了（收缩幅度为71±12%，而平行缓冲液处理的环为49±6%，n = 18，p < 0.01）。为了确定血小板介导的缺氧收缩增强的机制，血管环用吲哚美辛、血栓素A₂（TxA₂）/内过氧化物受体拮抗剂SQ29548、脂氧合酶抑制剂U60257B、游离氧自由基清除剂超氧化物歧化酶（SOD）加过氧化氢酶、5-羟色胺（S2）受体阻滞剂LY53857或ADP清除剂腺苷三磷酸双磷酸酶处理。尽管腺苷三磷酸双磷酸酶、U60257B、SQ29548、LY53857以及SOD加过氧化氢酶对血小板存在时的缺氧收缩增强没有影响，但用吲哚美辛处理可显著降低（p < 0.02）增强的缺氧血管收缩。由于吲哚美辛会降低血小板活化因子（PAF）的活性，血管环用两种不同的特异性PAF受体拮抗剂：L-659989和WEB 2170 BS处理。这两种药物都阻断了血小板增强的缺氧血管收缩。此外，合成PAF（10⁻⁷和10⁻⁶ M）本身可增强缺氧收缩，模拟血小板的活性。（摘要截短于250字）
