Background:

Ivabradine hydrochloride?is an orally bioavailable, hyperpolarization-activated, cyclic nucleotide-gated (HCN) channel blocker.

Ivabradine hydrochloride treatment (10 mg/kg/d) induces long-term HRR, and that improves diastolic LV function probably involving attenuated hypoxia, reduced remodeling, and/or preserved nitric oxide bioavailability, resulting from processes triggered early after HRR initiation: angiogenesis and/or preservation of endothelial nitric oxide synthase expression[1]. Ivabradine hydrochloride leads to a sustained 15-20% heart rate reduction, but has no effect on blood pressure. While ivabradine has no effect on endothelial function and vascular reactive oxygen species production in angiotensin II-treated rats, it improves both parameters in ApoE knockout mice. Ivabradine hydrochloride treatment leads to an attenuation of angiotensin II signaling and increased the expression of telomere-stabilizing proteins in ApoE knockout mice, which may explain its beneficial effects on the vasculature. The absence of these protective ivabradine effects in angiotensin II-infused rats may relate to the treatment duration or the presence of arterial hypertension[2].

参考文献:
[1]. Fang, Y., et al. Heart rate reduction induced by the if current inhibitor ivabradine improves diastolic function and attenuates cardiac tissue hypoxia. J Cardiovasc Pharmacol, 2012. 59(3): p. 260-7.
[2]. Kroller-Schon, S., et al. Differential effects of heart rate reduction with ivabradine in two models of endothelial dysfunction and oxidative stress. Basic Res Cardiol, 2011. 106(6): p. 1147-58.