Terutroban, a thromboxane/prostaglandin endoperoxide receptor antagonist, increases survival in stroke-prone rats by preventing systemic inflammation and endothelial dysfunction: comparison with aspirin and rosuvastatin.
J Pharmacol Exp Ther
; 334(1): 199-205, 2010 Jul.
Article
em En
| MEDLINE
| ID: mdl-20332187
ABSTRACT
This study investigated the efficacy of terutroban, a specific thromboxane/prostaglandin endoperoxide receptor antagonist, on stroke incidence in spontaneously hypertensive stroke-prone rats (SHRSP). The effects of terutroban were compared with those of aspirin, another antiplatelet agent, and rosuvastatin, known to exert end-organ protection in SHRSP. Salt-loaded male SHRSP were treated orally once a day with vehicle, terutroban (30 mg/kg/day), aspirin (60 mg/kg/day), or rosuvastatin (10 mg/kg/day). Compared with vehicle, and regardless of any effect on blood pressure or serum thromboxane B(2) levels, terutroban significantly increased survival (p < 0.001) as a consequence of a delayed brain lesion occurrence monitored by magnetic resonance imaging (p < 0.001), and a delayed increase of proteinuria (p < 0.001). Terutroban decreased cerebral mRNA transcription of interleukin-1beta, transforming growth factor-beta, and monocyte chemoattractant protein-1 after 6 weeks of dietary treatment. Terutroban also prevented the accumulation of urinary acute-phase proteins at high molecular weight, identified as markers of systemic inflammation, and assessed longitudinally by one-dimensional electrophoresis. Terutroban also has protective effects on the vasculature as suggested by the preservation of endothelial function and endothelial nitric-oxide synthase expression in isolated carotid arteries. These effects are similar to those obtained with rosuvastatin, and superior to those of aspirin. Terutroban increases survival in SHRSP by reducing systemic inflammation as well as preserving endothelial function. These data support clinical development of terutroban in the prevention of cerebrovascular and cardiovascular complications of atherothrombosis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Propionatos
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Receptores de Prostaglandina
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Endotélio Vascular
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Receptores de Tromboxanos
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Síndrome de Resposta Inflamatória Sistêmica
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Substâncias Protetoras
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Acidente Vascular Cerebral
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Hipertensão
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Naftalenos
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
J Pharmacol Exp Ther
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Itália