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
Articolo
Data di Pubblicazione:
2010
Citazione:
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 / P. Gelosa, R. Ballerio, C. Banfi, E. Nobili, A. Gianella, A. Pignieri, M. Brioschi, U. Guerrini, L. Castiglioni, V. Blanc-Guillemaud, L. Lerond, E. Tremoli, L. Sironi. - In: JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS. - ISSN 0022-3565. - 334:1(2010), pp. 199-205. [10.1124/jpet.110.165787]
Abstract:
This study investigated the efficacy of terutroban, a specific thromboxane/prostaglandin endoperoxide receptor antagonist, on stroke incidence in spontaneously hypertensive strokeprone
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. Saltloaded
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
B2 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-1 , transforming
growth factor- , 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.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
P. Gelosa, R. Ballerio, C. Banfi, E. Nobili, A. Gianella, A. Pignieri, M. Brioschi, U. Guerrini, L. Castiglioni, V. Blanc Guillemaud, L. Lerond, E. Tremoli, L. Sironi
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