BACKGROUND: Nebivolol is a new beta1-selective adrenergic receptor antagonist with a direct vasorelaxant effect that involves activation of the l-arginine-nitric oxide (NO) pathway. Therefore, treatment with nebivolol may protect against endothelial injury in hypertension. OBJECTIVE: To investigate whether chronic selective beta1-blockade with nebivolol could prevent endothelial dysfunction in salt-induced hypertension, and to compare it with atenolol. METHODS: Dahl salt-sensitive rats were treated for 8 weeks with standard chow or chow containing 4% NaCl alone or in combination with nebivolol (10 mg/kg per day) or atenolol (100 mg/kg per day). Isometric tension was continuously recorded in isolated aorta and small mesenteric arteries. Constitutive NO synthase (cNOS) activity was determined by [3H]citrulline assay. RESULTS: Chronic salt administration increased systolic blood pressure by 38 +/- 5 mmHg in salt-treated rats as compared with that in control rats. Both nebivolol and atenolol prevented a salt-induced increase in pressure. cNOS activity was significantly decreased by a high-salt diet. The impairment of endothelium-dependent relaxations in response to acetylcholine in salt-treated rats was prevented only by nebivolol, in both large and small arteries. In contrast, the reduced endothelium-independent relaxations and contractions in response to sodium nitroprusside and endothelin-1, respectively, were restored by both drugs. Nebivolol, but not atenolol, restored cNOS activity. CONCLUSIONS: Despite nebivolol and atenolol having the same blood-pressure-decreasing effect, only nebivolol was able to prevent endothelial dysfunction. This study demonstrates for the first time that the acute NO-mediated vasodilatory action of nebivolol is also present during chronic treatment. Hence, nebivolol might become a new therapeutic tool with which to exert vascular protective effects against end-organ damage in conditions associated with NO deficiency.
BACKGROUND:Nebivolol is a new beta1-selective adrenergic receptor antagonist with a direct vasorelaxant effect that involves activation of the l-arginine-nitric oxide (NO) pathway. Therefore, treatment with nebivolol may protect against endothelial injury in hypertension. OBJECTIVE: To investigate whether chronic selective beta1-blockade with nebivolol could prevent endothelial dysfunction in salt-induced hypertension, and to compare it with atenolol. METHODS:Dahl salt-sensitive rats were treated for 8 weeks with standard chow or chow containing 4% NaCl alone or in combination with nebivolol (10 mg/kg per day) or atenolol (100 mg/kg per day). Isometric tension was continuously recorded in isolated aorta and small mesenteric arteries. Constitutive NO synthase (cNOS) activity was determined by [3H]citrulline assay. RESULTS: Chronic salt administration increased systolic blood pressure by 38 +/- 5 mmHg in salt-treated rats as compared with that in control rats. Both nebivolol and atenolol prevented a salt-induced increase in pressure. cNOS activity was significantly decreased by a high-salt diet. The impairment of endothelium-dependent relaxations in response to acetylcholine in salt-treated rats was prevented only by nebivolol, in both large and small arteries. In contrast, the reduced endothelium-independent relaxations and contractions in response to sodium nitroprusside and endothelin-1, respectively, were restored by both drugs. Nebivolol, but not atenolol, restored cNOS activity. CONCLUSIONS: Despite nebivolol and atenolol having the same blood-pressure-decreasing effect, only nebivolol was able to prevent endothelial dysfunction. This study demonstrates for the first time that the acute NO-mediated vasodilatory action of nebivolol is also present during chronic treatment. Hence, nebivolol might become a new therapeutic tool with which to exert vascular protective effects against end-organ damage in conditions associated with NO deficiency.
Authors: Jasmina Varagic; Sarfaraz Ahmad; K Bridget Brosnihan; Javad Habibi; Roger D Tilmon; James R Sowers; Carlos M Ferrario Journal: Am J Nephrol Date: 2010-11-02 Impact factor: 3.754
Authors: Frank T Spradley; Dao H Ho; Kyu-Tae Kang; David M Pollock; Jennifer S Pollock Journal: Am J Physiol Regul Integr Comp Physiol Date: 2011-10-26 Impact factor: 3.619
Authors: Julieta S Del Mauro; Paula D Prince; Yanina Santander Plantamura; Miguel A Allo; Luciano Parola; Nahuel Fernandez Machulsky; Marcela A Morettón; Eliana P Bin; Germán E González; Facundo M Bertera; Andrea Carranza; Gabriela Berg; Carlos A Taira; Martín Donato; Diego A Chiappetta; Ariel H Polizio; Christian Höcht Journal: Hypertens Res Date: 2021-02-22 Impact factor: 3.872