Nitric-oxide-mediated relaxations in salt-induced hypertension: Effect of chronic β1-selective receptor blockade
2002
Background Nebivolol is a new β 1 -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 β 1 -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% NaCI 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 [ 3 H]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.
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