Hypertension induces
left-ventricular hypertrophy (LVH) by mechanisms involving oxidative stress and unbalanced cardiac
matrix metalloproteinase (
MMP) activity. We hypothesized that β1-adrenergic receptor blockers with
antioxidant properties (
nebivolol) could reverse
hypertension-induced LVH more effectively than conventional β1-blockers (
metoprolol) when used at doses that exert similar
antihypertensive effects. Two-kidney one-
clip (2K1C)
hypertension was induced in male Wistar rats. Six weeks after surgery, hypertensive and
sham rats were treated with
nebivolol (10 mg kg(-1)day(-1)) or
metoprolol (20 mg kg(-1)day(-1)) for 4 weeks. Systolic blood pressure was monitored weekly by tail-cuff plethysmography. LV structural changes and
fibrosis were studied in
hematoxylin/
eosin- and picrosirius-stained sections, respectively. Cardiac
MMP levels and activity were determined by in situ zymography, gel zymography, and immunofluorescence.
Dihydroethidium and
lucigenin-derived chemiluminescence assays were used to assess cardiac
reactive oxygen species (ROS) production.
Nitrotyrosine levels were determined in LV samples by immunohistochemistry and green fluorescence and were evaluated using the ImageJ software. Cardiac
protein kinase B/Akt (AKT) phosphorylation state was assessed by Western blot. Both β-blockers exerted similar
antihypertensive effects and attenuated
hypertension-induced cardiac remodeling. Both drugs reduced myocyte
hypertrophy and
collagen deposition in 2K1C rats. These effects were associated with lower cardiac ROS and
nitrotyrosine levels and attenuation of
hypertension-induced increases in cardiac MMP-2 levels and in situ gelatinolytic activity
after treatment with both β-blockers. Whereas
hypertension increased AKT phosphorylation, no effects were found with β-blockers. In conclusion, we found evidence that two β1-blockers with different properties attenuate
hypertension-induced LV
hypertrophy and cardiac
collagen deposition in association with significant cardiac
antioxidant effects and MMP-2 downregulation, thus suggesting a critical role for β1-adrenergic receptors in mediating those effects.
Nebivolol is not superior to
metoprolol, at least with respect to their capacity to reverse
hypertension-induced LVH.