Nebivolol attenuates prooxidant and profibrotic mechanisms involving TGF-ß and MMPs, and decreases vascular remodeling in renovascular hypertension.
Free Radic Biol Med
; 65: 47-56, 2013 Dec.
Article
em En
| MEDLINE
| ID: mdl-23806385
ABSTRACT
Nebivolol and metoprolol are ß1-adrenergic receptor blockers with different properties. We hypothesized that nebivolol, but not metoprolol, could attenuate prooxidant and profibrotic mechanisms of hypertension and therefore protect against the vascular remodeling associated with hypertension. Hypertension was induced in male Wistar rats by clipping the left renal artery. 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. Morphologic changes in the aortic wall were studied in hematoxylin/eosin and picrosirius red sections. Aortic NAD(P)H activity and superoxide production were evaluated by luminescence and dihydroethidium, respectively, and TBARS levels were measured in plasma. Aortic nitrotyrosine staining was evaluated to assess peroxynitrite formation. TGF-ß levels and p-ERK 1/2 expression were determined by immunofluorescence and Western blotting, respectively. Matrix metalloproteinase (MMP) activity and expression were determined by in situ zymography, gel zymography, Western blotting, and immunofluorescence, and TIMP-1 was assessed by immunohistochemistry. Both ß1-receptor antagonists exerted very similar antihypertensive effects. However, while metoprolol had no significant effects, nebivolol significantly attenuated vascular remodeling and collagen deposition associated with hypertension. Moreover, nebivolol, but not metoprolol, attenuated hypertension-induced increases in aortic NAD(P)H oxidase activity, superoxide production, TBARS concentrations, nitrotyrosine levels, TGF-ß upregulation, and MMP-2 and -9 expression/activity. No effects on p-ERK 1/2 and TIMP-1 expression were found. These results show for the first time that nebivolol, but not metoprolol, attenuates prooxidant and profibrotic mechanisms involving TGF-ß and MMP-2 and MMP-9, which promote vascular remodeling in hypertension.
Palavras-chave
2 kidney, one clip; 2K1C; DHE; ECM; ERK 1/2; MMP; Matrix metalloproteinases; Metoprolol; Nebivolol; Oxidative stress; Renovascular hypertension; SBP; TBARS; TGF; Vascular remodeling; dihydroethidium; extracellular matrix; extracellular regulated kinase 1/2; matrix metalloproteinase; systolic blood pressure; thiobarbituric acid-reactive substances; transforming grown factor
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Benzopiranos
/
Etanolaminas
/
Remodelação Vascular
/
Hipertensão Renovascular
/
Antioxidantes
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Free Radic Biol Med
Assunto da revista:
BIOQUIMICA
/
MEDICINA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Brasil