Heart rate reduction with ivabradine improves erectile dysfunction in parallel to decrease in atherosclerotic plaque load in ApoE-knockout mice

Heart rate reduction with ivabradine promotes shear stress-dependent anti-inflammatory mechanisms in arteries

“…In particular, ivabradine prevented renal and cerebral endothelial dysfunction in a mouse transgenic model of mild dyslipidaemia 11 and prevented atherosclerotic lesion formation 13 and improved erectile function 12 in hypercholesterolemic ApoE -/-mice. The underlying mechanism has remained elusive because ivabradine-targets have not been identified in vascular cells and ivabradine did not influence plasma lipid levels 11,13 .…”

“…Ivabradine treatment has been used successfully to treat coronary artery disease 8,9 and can also reduce atherosclerosis in experimental models [11][12][13] . In particular, ivabradine prevented renal and cerebral endothelial dysfunction in a mouse transgenic model of mild dyslipidaemia 11 and prevented atherosclerotic lesion formation 13 and improved erectile function 12 in hypercholesterolemic ApoE -/-mice.…”

“…The administration of ivabradine reduced experimental atherosclerosis in hyperlipidaemic murine 13 and rabbit models 14 . However, molecular targets of ivabradine have not been identified in vascular cells and the atheroprotective effects of ivabradine are not due to a lipid-lowering effect of ivabradine, since the drug had no effects on cholesterol levels [11][12][13] . Taken together, these experiments suggest that a direct effect of ivabradine on vessels is unlikely, and suggest that reduction of heart rate may be a primary mechanism of action of the drug.…”

“…Despite this, a recent study found that ivabradine did not have beneficial effects in patients with stable coronary artery disease but without heart failure 10 , suggesting that its vasculoprotective effects may be restricted to patients with heart failure. The mechanism for the protective effects of ivabradine has been studied using animal models [11][12][13][14] . The administration of ivabradine reduced experimental atherosclerosis in hyperlipidaemic murine 13 and rabbit models 14 .…”

Ivabradine therapy and correction of the target organ pathology in patients with ischemic chronic heart failure

“…Так в работе F. Custodis et al установлено, что снижение ЧСС с помощью 6-недельного применения ивабрадина уменьшает выработку маркеров оксидативного стресса, улуч-шает функцию эндотелия и уменьшает размеры ате-росклеротической бляшки у мышей независимо от АД и уровня липидов [26]. M. Baumh kel et al пока-зали, что у мышей на фоне эндотелиальной дисфунк-ции, индуцированной диетой с высоким содержа-нием холестерина, 3-месячная терапия ивабрадином способствует уменьшению размеров атеросклероти-ческих бляшек и улучшению эндотелиальной дис-функции [27]. A. Dominguez-Rodriguez et al также отметили при применении ивабрадина уменьшение размеров атеросклеротических бляшек у экспери-ментальных животных на фоне липид-индуцирован-ного атеросклероза [28].…”