Abstract 393: Chronic Nebivolol Treatment Attenuates MMP Activity and Oxidative Stress and Improves Renovascular Hypertension-induced Cardiac Hypertrophy

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Abstract

Nebivolol (Nebi) is the most selective cardiac β1-adrenergic receptor blocker and exerts antioxidant effects. Reactive oxygen species (ROS) enhance cardiac matrix metalloproteinase activity (MMPs) and contribute to hypertension-induced left ventricular hypertrophy (LVH). However, it is uncertain whether Nebi decreases MMP-2 levels and cardiac remodeling associated with hypertension as a result of its antioxidant properties. Hypertension was induced by clipping the left renal artery (2K1C). Six weeks after surgery, hypertensive and sham rats were treated with Nebi, Metoprolol (Meto) or Vehicle (by gavage) for four weeks. Systolic blood pressure (SBP) was monitored weekly by tail-cuff plethysmography. LV structural changes were studied in hematoxylin/eosin sections. MMP levels and activity were determined by immunofluorescence and in situ zymography. ROS and nitrotyrosine levels were evaluated by dihydroethidium and immunohistochemistry, respectively. Similar reduction in SBP was found with both treatments (202±5 mmHg in 2K1C+Vehicle versus 161±19 and 162±18 mmHg in 2K1C Nebi or Meto groups, respectively; P<0.05). Both treatments reduced LV remodeling and ROS formation (P<0.05). Both drugs decreased nitrotyrosine levels (3.9±0.2, 2.3±0.3, and 2.4±0.3 arbitrary units, respectively in 2K1C+vehicle, 2K1C+Meto, and 2K1C+Nebi groups, respectively; P<0.05). Increased MMP-2 levels (16.0±2.0 versus 7.0±0.9 arbitrary units; P<0.05) and activity (8.0±0.4 versus 6.0±0.1 arbitrary units; P<0.05) were observed in the 2K1C+vehicle group when compared to the sham group. These alterations were normalized by both treatments (similar levels to those found in the sham group). No significant changes were observed in the sham groups. These findings suggest that different β-blockers exert important antioxidant effects that may underlie the lower LV MMP activity and cardiac remodeling in 2K1C hypertension.

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