Ishizuka Toshiaki, Niwa Atsuko, Tabuchi Masaki, Nagatani Yusuke, Ooshima Kana, Higashino Hideaki
Department of Pharmacology, Kinki University School of Medicine, Ohno-Higashi, Osaka, Japan.
J Hypertens. 2007 Apr;25(4):861-70. doi: 10.1097/HJH.0b013e3280464dc8.
Inflammatory processes may play a pivotal role in the pathogenesis of cerebrovascular injury in salt-loaded, stroke-prone, spontaneously hypertensive rats (SHRSP). Thromboxane A2 (TP) receptor stimulation by 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) is involved in the process of vascular inflammation.
In the present study, we examined the involvement of TP receptor in the development of cerebrovascular damage in salt-loaded SHRSP.
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-PGF2alpha infusion on cerebrovascular injury of SHRSP.
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-PGF2alpha-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-PGF2alpha-treated SHRSP.
These results suggest that TP receptor stimulation by 8-iso-PGF2alpha may involve salt loading-induced stroke through activation of cerebrovascular inflammation and damage.
炎症过程可能在盐负荷、易中风、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-异前列腺素F2α（8-iso-PGF2α）刺激血栓素A2（TP）受体参与血管炎症过程。
在本研究中，我们检测了TP受体在盐负荷SHRSP脑血管损伤发展中的作用。
9周龄的SHRSP喂食0.4% NaCl或4% NaCl饮食，同时给予或不给予ONO-8809治疗（一种TP受体拮抗剂），持续5周。比较各组之间的血压、死亡率以及脑血管炎症和损伤参数。此外，我们检测了8-iso-PGF2α输注对SHRSP脑血管损伤的影响。
SHRSP高盐摄入显著增加血脑屏障损伤和早期死亡率，ONO-8809治疗可抑制这些情况，且与血压变化无关。盐负荷还显著增加SHRSP基底动脉中的超氧化物生成，ONO-8809治疗可抑制这一现象。ONO-8809治疗显著降低了盐负荷SHRSP和8-iso-PGF2α治疗的SHRSP中风病变对侧大脑皮质中风阴性区域的巨噬细胞积聚和基质金属蛋白酶-9（MMP-9）活性。ONO-8809治疗可防止盐负荷SHRSP和8-iso-PGF2α治疗的SHRSP脑小动脉血管层变薄。
这些结果表明，8-iso-PGF2α刺激TP受体可能通过激活脑血管炎症和损伤参与盐负荷诱导的中风。
