Involvement of thromboxane A2 receptor in the cerebrovascular damage of salt-loaded, stroke-prone rats.

Abstract

BACKGROUND:

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.

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-PGF2alpha 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-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.

CONCLUSIONS:

These results suggest that TP receptor stimulation by 8-iso-PGF2alpha may involve salt loading-induced stroke through activation of cerebrovascular inflammation and damage.

• Authors: Toshiaki Ishizuka, Atsuko Niwa, Masaki Tabuchi, Yusuke Nagatani, Kana Ooshima, Hideaki Higashino
• Journal: Journal of hypertension (J Hypertens) Vol. 25 Issue 4 Pg. 861-70 (Apr 2007) ISSN: 0263-6352 [Print] England
• PMID: 17351380 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Bridged Bicyclo Compounds
• Chemokine CCL2
• Fatty Acids, Monounsaturated
• Receptors, Thromboxane A2, Prostaglandin H2
• Sodium Chloride, Dietary
• Vasoconstrictor Agents
• Superoxides
• ONO 8809
• 8-epi-prostaglandin F2alpha
• Dinoprost
• Matrix Metalloproteinase 9

Topics

• Analysis of Variance
• Animals
• Basilar Artery (drug effects, metabolism)
• Biomarkers (blood)
• Blood Pressure (drug effects)
• Blood-Brain Barrier (drug effects, metabolism)
• Bridged Bicyclo Compounds (pharmacology)
• Cerebral Arteries (drug effects, metabolism)
• Cerebral Cortex (drug effects, metabolism)
• Chemokine CCL2 (blood)
• Dinoprost (analogs & derivatives, pharmacology)
• Disease Models, Animal
• Fatty Acids, Monounsaturated (pharmacology)
• Macrophages (drug effects, metabolism)
• Male
• Matrix Metalloproteinase 9 (drug effects, metabolism)
• Rats
• Rats, Inbred SHR
• Receptors, Thromboxane A2, Prostaglandin H2 (antagonists & inhibitors, drug effects, metabolism)
• Sodium Chloride, Dietary (adverse effects)
• Stroke (etiology, metabolism, mortality, physiopathology)
• Superoxides (metabolism)
• Time Factors
• Tunica Media (drug effects, metabolism, physiopathology)
• Vasoconstrictor Agents (pharmacology)