XXXX down-regulates vascular matrix metalloproteinases and ameliorates @entity455 and remodelling in @entity2792 .

@entity455 @entity101 @entity35 @entity12149 @entity1711 @entity26 @entity409 @entity13373 @entity2792 @entity6929 @entity6175 @entity14568 @entity11017
BACKGROUND AND PURPOSE: Mounting evidence implicates matrix metalloproteinase (MMP) in the @entity455 and remodelling associated with @entity101 . We tested the hypothesis that treatment with @entity13373 ( @entity14568 ), which interferes with NF-kB-induced MMPs gene transcription, could exert antihypertensive effects, prevent @entity11017 and @entity6929 up-regulation, and protect against the functional alterations and vascular remodelling of two-kidney, one clip (2K1C) @entity101 . EXPERIMENTAL APPROACH: Sham-operated or @entity101 @entity35 were treated with vehicle or @entity14568 (100 mg  Kg(-1)   day(-1)) by gavage for 8 weeks. Systolic blood pressure (SBP) was monitored weekly. Aortic rings were isolated to assess endothelium-dependent relaxations. Quantitative morphometry of structural alterations of the aortic wall was carried out in @entity6175 / @entity1711 sections. Formation of vascular reactive @entity26 species (ROS), and inducible (i) NOS and phosphorylated- @entity12149 NF-kB subunit expression were measured in the aortas. @entity11017 and @entity6929 aortic levels and gelatinolytic activity were determined by gelatin and in situ zymography and by immunofluorescence. KEY RESULTS: Treatment with @entity14568 attenuated the increases in SBP and prevented the @entity409 associated with 2K1C @entity101 . Moreover, @entity14568 reversed the vascular aortic remodelling, the increases in aortic ROS levels and in iNOS and phosphorylated- @entity12149 NF-kB expression found in 2K1C @entity35 . These effects were associated with attenuation of 2K1C up-regulation of aortic @entity11017 and @entity6929 levels and gelatinolytic activity. CONCLUSION AND IMPLICATIONS: These findings suggest that @entity14568 down-regulates vascular MMPs and ameliorates @entity455 and remodelling in @entity2792 , thus providing evidence supporting the suggestion that @entity14568 is probably a good candidate to be used to treat @entity101 .
