Increased vascular
matrix metalloproteinases (
MMPs) levels play a role in late phases of hypertensive
vascular remodeling. However, no previous study has examined the time course of
MMPs in the various phases of two-kidney, one-
clip hypertension (2K1C). We examined structural vascular changes,
collagen and
elastin content, vascular oxidative stress, and
MMPs levels/activities during the development of 2K1C
hypertension. Plasma
angiotensin converting enzyme (ACE) activity was measured to assess renin-angiotensin system activation.
Sham or 2K1C hypertensive rats were studied after 2, 4, 6, and 10weeks of
hypertension. Systolic blood pressure (SBP) was monitored weekly. Morphometry of structural changes in the aortic wall was studied in
hematoxylin/
eosin,
orcein and
picrosirius red sections. Aortic
NADPH activity and
superoxide production was evaluated. Aortic gelatinolytic activity was determined by in situ zymography, and MMP-2, MMP-14, and tissue inhibitor of
MMPs (TIMP)-2 levels were determined by
gelatin zymography, immunofluorescence and immunohistochemistry. 2K1C
hypertension was associated with increased ACE activity, which decreased to normal after 10 weeks. We found increased aortic
collagen and
elastin content in the early phase of
hypertension, which were associated with vascular
hypertrophy, increased vascular MMP-2 and MMP-14 (but not TIMP-2) levels, and increased gelatinolytic activity, possibly as a result of increased vascular
NADPH oxidase activity and oxidative stress. These results indicate that
vascular remodeling of
renovascular hypertension is an early process associated with early increases in
MMPs activities, enhanced matrix deposition and oxidative stress. Using
antioxidants or
MMPs inhibitors in the early phase of
hypertension may prevent the vascular alterations of
hypertension.