Nitric-oxide-mediated relaxations in salt-induced hypertension: Effect of chronic β1-selective receptor blockade

Francesco Cosentino, Sandro Bonetti, Rudolf Rehorik, Masato Eto, Gabriele Werner-Felmayer, Massimo Volpe, Thomas F. Lüscher

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Nebivolol is a new β1-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 β1-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.

Original languageEnglish
Pages (from-to)421-428
Number of pages8
JournalJournal of Hypertension
Volume20
Issue number3
DOIs
Publication statusPublished - Mar 2002

Keywords

  • β-adrenergic receptor blockade
  • Endothelial function
  • Hypertension
  • Nitric oxide

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

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