Titre du document / Document title

Impact of β-Adrenoceptor antagonists on myofilament calcium sensitivity of rabbit and human myocardium

Auteur(s) / Author(s)

ZEITZ O. ⁽¹⁾ ; RAHMAN A. ⁽¹⁾ ; HASENFUSS G. ⁽¹⁾ ; JANSSEN P. M. L. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Department of Cardiology and Pneumology, University of Göttingen, Göttingen, ALLEMAGNE

Résumé / Abstract

β-Adrenoceptor antagonists (β-blockers) are commonly used in clinical pharmacotherapy of cardiovascular diseases. Carvedilol and nebivolol possess beneficial effects on myocardial function in situations of oxidative stress associated with intracellular calcium overload. This preservation of contractile function might be due to direct scavenging capacities or to compensation of the intracellular calcium overload through direct impact on myofilament calcium sensitivity. Accordingly, we measured the relation between calcium and force in the absence and in the presence of 10^-6M carvedilol, nebivolol, or propranolol in skinned right ventricular trabeculae of rabbit hearts. In rabbit myocardium, nebivolol (10^-6 M) altered the pCa_50% by a rightward shift (less sensitive) from 5.72 ± 0.05 to 5.57 ± 0.05 (p < 0.05). Maximal force development was reduced by nebivolol. In contrast, the same concentration of propranolol or carvedilol did not influence calcium sensitivity and force development. In additional experiments, we repeated this protocol in trabeculae from human failing hearts. As in rabbit trabeculae, nebivolol shifted the pCa_50% by 0.16 ± 0.04 pCa units to the right (p < 0.05). Experiments with intact rabbit trabeculae confirmed depressed contractility: when all β-adrenoceptors were blocked by 10^-6 M propranolol, subsequent addition of 10^-6 M nebivolol reduced developed force of these muscles significantly from 3.1 ± 0.9 to 1.7 ± 0.4 mN/mm². We conclude that nebivolol desensitizes cardiac myofilaments slightly, whereas neither propranolol nor carvedilol had an effect.

Revue / Journal Title

Journal of cardiovascular pharmacology   ISSN 0160-2446   CODEN JCPCDT 

Source / Source

2000, vol. 36, n^o1, pp. 126-131 (29 ref.)

Langue / Language

Anglais

Editeur / Publisher

Lippincott, Hagerstown, MD, ETATS-UNIS  (1979) (Revue)

Mots-clés anglais / English Keywords

Carvedilol ; Beta blocking agent ; Nebivolol ; Propranolol ; Myocardium ; Circulatory system ; Heart ; Comparative study ; Calcium ; Sensitivity ; Mechanism of action ; Biological activity ; Myofibril ; Animal ; Rabbit ; In vitro ; Right ventricle ; Human ; Lagomorpha ; Mammalia ; Vertebrata ;

Mots-clés français / French Keywords

Carvédilol ; Bloquant β-adrénergique ; Nébivolol ; Propranolol ; Myocarde ; Appareil circulatoire ; Coeur ; Etude comparative ; Calcium ; Sensibilité ; Mécanisme action ; Activité biologique ; Myofibrille ; Animal ; Lapin ; In vitro ; Ventricule droit ; Homme ; Lagomorpha ; Mammalia ; Vertebrata ;

Mots-clés espagnols / Spanish Keywords

Carvedilol ; Bloqueador β-adrenérgico ; Nebivolol ; Propranolol ; Miocardio ; Aparato circulatorio ; Corazón ; Estudio comparativo ; Calcio ; Sensibilidad ; Mecanismo acción ; Actividad biológica ; Miofibrilla ; Animal ; Conejo ; In vitro ; Ventrículo derecho ; Hombre ; Lagomorpha ; Mammalia ; Vertebrata ;

Localisation / Location

INIST-CNRS, Cote INIST : 18065, 35400009017204.0170