Involvement of thromboxane A2 receptor in the cerebrovascular damage of salt-loaded, stroke-prone rats
Involvement of thromboxane A2 receptor in the cerebrovascular damage of salt-loaded, stroke-prone rats
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DOI：
10.1097/hjh.0b013e3280464dc8
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发表时间：
2007-04-01
影响因子：
4.9
通讯作者：
Higashino, Hideaki
中科院分区：
文献类型：
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作者：
Ishizuka, Toshiaki;Niwa, Atsuko;Higashino, Hideaki
炎症过程可能在盐负荷、卒中易发、自发性高血压大鼠（SHRSP）脑血管损伤的发病机制中起关键作用。8-iso-前列腺素F-2 α (8-iso-PGF(2 α))刺激血栓素A(2) （TP）受体参与了血管炎症的过程。目的探讨TP受体在盐负荷大鼠脑血管损伤发生中的作用。方法9周龄的SHRSP分别饲喂0.4% NaCl和4% NaCl饲粮，同时添加或不添加ONO-8809 （TP受体拮抗剂）处理5周。比较两组血压、死亡率、脑血管炎症及损伤参数。此外，我们还研究了8-iso-PGF（2 α）输注对SHRSP脑血管损伤的影响。结果高盐摄入显著增加了SHRSP患者的血脑屏障损伤和早期死亡率，而ONO-8809治疗可抑制这种损伤，而不依赖于血压的变化。盐负荷还显著增加了SHRSP基底动脉中超氧化物的产生，而ONO-8809处理抑制了这一现象。ONO-8809可显著降低盐负荷SHRSP和8-iso-PGF（2 α）处理SHRSP脑卒中病变对侧大脑皮层卒中阴性区巨噬细胞积累和基质金属蛋白酶-9 （MMP-9）活性。ONO-8809处理可防止盐负载SHRSP和8-iso-PGF（2 α）处理的SHRSP脑小动脉血管层变薄。结论8-iso-PGF（2 α）对TP受体的刺激可能通过激活脑血管炎症和损伤参与盐负荷引起的脑卒中。
Background Inflammatory processes may play a pivotal role in the pathogenesis of cerebrovascular injury in salt-loaded, stroke-prone, spontaneously hypertensive rats (SHRSP). Thromboxane A(2) ( TP) receptor stimulation by 8-iso-prostaglandin F-2 alpha (8-iso-PGF(2 alpha)) is involved in the process of vascular inflammation.Objective In the present study, we examined the involvement of TP receptor in the development of cerebrovascular damage in salt-loaded SHRSP.Methods Nine-week-old SHRSP were fed a 0.4% NaCl or a 4% NaCl diet with or without ONO-8809 treatment (a TP receptor antagonist) for 5 weeks. Blood pressure, mortality, and the parameters of cerebrovascular inflammation and damage were compared between the groups. Moreover, we examined the effect of 8-iso-PGF(2 alpha) infusion on cerebrovascular injury of SHRSP.Results High salt intake in SHRSP significantly increased blood - brain barrier impairment and early mortality, which were suppressed by ONO-8809 treatment independent of changes in blood pressure. Salt loading also significantly increased superoxide production in basilar arteries of SHRSP, which was suppressed by ONO-8809 treatment. Macrophage accumulation and matrix metalloproteinase-9 (MMP-9) activity in the stroke-negative area in the contralateral cerebral cortex to the stroke lesion of salt-loaded SHRSP and 8-iso-PGF(2 alpha)-treated SHRSP were significantly reduced by ONO-8809 treatment. The ONO-8809 treatment prevented thinning of the vessel layer in cerebral arterioles of salt- loaded SHRSP and 8-iso-PGF(2 alpha)-treated SHRSP.Conclusions These results suggest that TP receptor stimulation by 8-iso-PGF(2 alpha) may involve salt loading-induced stroke through activation of cerebrovascular inflammation and damage.