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 language | English |
|---|---|
| Pages (from-to) | 421-428 |
| Number of pages | 8 |
| Journal | Journal of Hypertension |
| Volume | 20 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 2002 |
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Keywords
- β-adrenergic receptor blockade
- Endothelial function
- Hypertension
- Nitric oxide
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology
Cite this
Nitric-oxide-mediated relaxations in salt-induced hypertension : Effect of chronic β1-selective receptor blockade. / Cosentino, Francesco; Bonetti, Sandro; Rehorik, Rudolf; Eto, Masato; Werner-Felmayer, Gabriele; Volpe, Massimo; Lüscher, Thomas F.
In: Journal of Hypertension, Vol. 20, No. 3, 03.2002, p. 421-428.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nitric-oxide-mediated relaxations in salt-induced hypertension
T2 - Effect of chronic β1-selective receptor blockade
AU - Cosentino, Francesco
AU - Bonetti, Sandro
AU - Rehorik, Rudolf
AU - Eto, Masato
AU - Werner-Felmayer, Gabriele
AU - Volpe, Massimo
AU - Lüscher, Thomas F.
PY - 2002/3
Y1 - 2002/3
N2 - 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.
AB - 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.
KW - β-adrenergic receptor blockade
KW - Endothelial function
KW - Hypertension
KW - Nitric oxide
UR - http://www.scopus.com/inward/record.url?scp=0036492018&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036492018&partnerID=8YFLogxK
U2 - 10.1097/00004872-200203000-00017
DO - 10.1097/00004872-200203000-00017
M3 - Article
C2 - 11875309
AN - SCOPUS:0036492018
VL - 20
SP - 421
EP - 428
JO - Journal of Hypertension
JF - Journal of Hypertension
SN - 0263-6352
IS - 3
ER -