title: 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.affiliation: Department of Pharmacology, Kinki University School of Medicine, Ohno-Higashi, Osaka, Japan. ishizuka@med.kindai.ac.jp
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Ishizuka
authors.forename: Atsuko
authors.initials: A
authors.lastname: Niwa
authors.forename: Masaki
authors.initials: M
authors.lastname: Tabuchi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nagatani
authors.forename: Kana
authors.initials: K
authors.lastname: Ooshima
authors.forename: Hideaki
authors.initials: H
authors.lastname: Higashino
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D018932:Chemokine CCL2 / Q000097:blood; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D020521:Stroke / Q000209:etiology* / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D017540:Tunica Media / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D001643:Bridged Bicyclo Compounds; D018932:Chemokine CCL2; D005229:Fatty Acids, Monounsaturated; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D017673:Sodium Chloride, Dietary; D014662:Vasoconstrictor Agents; D013481:Superoxides; C067427:ONO 8809; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D020780:Matrix Metalloproteinase 9