Modulation of Sympathetic Activity and Innervation With Chronic Ivabradine and β-Blocker Therapies: Analysis of Hypertensive Rats With Heart Failure

Journal of Cardiovascular Pharmacology and Therapeutics
Kazuyoshi KakehiShunichi Miyazaki

Abstract

Whether the reduction of heart rate with ivabradine (IVA) could affect sympathetic activation and cardiac innervation in heart failure (HF) remains unknown. The present study assessed the chronic effects of IVA and β-blocker on the systemic and local sympathetic nervous systems of hypertensive animals with HF. 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 tyr...Continue Reading

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Citations

Mar 2, 2021·Frontiers in Cardiovascular Medicine·Fedor Simko, Tomas Baka

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BETA
PCR

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