Modulation of Sympathetic Activity and Innervation With Chronic Ivabradine and ß-Blocker Therapies: Analysis of Hypertensive Rats With Heart Failure.
J Cardiovasc Pharmacol Ther
; 24(4): 387-396, 2019 07.
Article
en En
| MEDLINE
| ID: mdl-30786751
ABSTRACT
BACKGROUND:
Whether the reduction of heart rate with ivabradine (IVA) could affect sympathetic activation and cardiac innervation in heart failure (HF) remains unknown.PURPOSE:
The present study assessed the chronic effects of IVA and ß-blocker on the systemic and local sympathetic nervous systems of hypertensive animals with HF. METHODS ANDRESULTS:
The Dahl salt-sensitive rats received chronic IVA, bisoprolol (BIS), or placebo (CTL) therapy. The survival of the animal models with IVA and BIS significantly improved (median; 19.7 in IVA and 19.7 in BIS vs 17.0 weeks in CTL, P < .001). A similar decrease in 24-hour heart rate (mean; 305 in IVA and 329 in BIS vs 388 beats/min in CTL, P < .001) without effect on blood pressure, and an improvement in the left ventricular dysfunction (mean fractional shortening; 56.7% in IVA and 47.8% in BIS vs 39.0% in CTL, P < .001) were observed in the animals with IVA and BIS. However, a negative inotropic effect was only observed in the animals with BIS. Excessive urinary noradrenaline excretion in animals with CTL was only suppressed with the use of IVA (mean; 1.35 µg/d in IVA and 1.95 µg/d in BIS vs 2.27 µg/d in CTL, P = .002). In contrast, atrial noradrenaline and acetylcholine depletion in the animals with CTL improved and the tyrosine hydroxylase expression in the both atria were restored with the use of both IVA and BIS.CONCLUSIONS:
IVA therapy improved the survival of hypertensive animals with HF. Furthermore, it was associated with the amelioration of systemic sympathetic activation and cardiac sympathetic and parasympathetic nerve innervations. Chronic ß-blocker therapy with negative inotropic effects had beneficial effects only on cardiac innervations.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sistema Nervioso Simpático
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Fármacos Cardiovasculares
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Bisoprolol
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Antagonistas de Receptores Adrenérgicos beta 1
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Ivabradina
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Corazón
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Insuficiencia Cardíaca
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Hipertensión
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
J Cardiovasc Pharmacol Ther
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
FARMACOLOGIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón