Involvement of thromboxane A(2) receptor in the cerebrovascular damage of salt-loaded, stroke-prone rats

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.