The
vascular remodeling associated with
hypertension involves oxidative stress and enhanced
matrix metalloproteinases (
MMPs) expression/activity, especially MMP-2. While previous work showed that
lercanidipine, a third-generation
dihydropyridine calcium channel blocker (CCB), attenuated the oxidative stress and increased MMP-2 expression/activity in two-kidney, one-
clip (2K1C)
hypertension, no previous study has examined whether first- or second-generation
dihydropyridines produce similar effects. We compared the effects of
nifedipine,
nimodipine, and
amlodipine on 2K1C
hypertension-induced changes in systolic blood pressure (SBP),
vascular remodeling, oxidative stress, and
MMPs levels/activity.
Sham-operated and 2K1C rats were treated with water,
nifedipine 10 mg/kg/day,
nimodipine 15 mg/kg/day, or
amlodipine 10 mg/kg/day by gavage, starting 3 weeks after
hypertension was induced. SBP was monitored weekly. After 6 weeks of treatment, quantitative morphometry of structural changes in the aortic wall was studied in
hematoxylin/
eosin-stained sections. Aortic and systemic
reactive oxygen species levels were measured by using
dihydroethidine and
thiobarbituric acid-reactive substances (
TBARs), respectively. Aortic MMP-2 levels and activity were determined by
gelatin zymography, in situ zymography, and immunofluorescence.
Nifedipine,
nimodipine, or
amlodipine attenuated the increases in SBP in hypertensive rats by approximately 17% (P < 0.05) and prevented vascular
hypertrophy (P < 0.05). These CCBs blunted 2K1C-induced increases in vascular oxidative stress and plasma
TBARs concentrations (P < 0.05). All
dihydropyridines attenuated the increases in aortic MMP-2 levels and activity associated with 2K1C
hypertension. These findings suggest lack of superiority of one particular
dihydropyridine, at least with respect to
antioxidant effects,
MMPs downregulation, and inhibition of
vascular remodeling in
hypertension.