Differential effects of heart rate reduction with ivabradine in two models of endothelial dysfunction and oxidative stress.
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Differential effects of heart rate reduction with ivabradine in two models of endothelial dysfunction and oxidative stress. / Kröller-Schön, Swenja; Schulz, Eberhard; Wenzel, Philip; Kleschyov, Andrei L; Hortmann, Marcus; Torzewski, Michael; Oelze, Matthias; Renné, Thomas; Daiber, Andreas; Münzel, Thomas.
In: BASIC RES CARDIOL, Vol. 106, No. 6, 6, 2011, p. 1147-1158.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Differential effects of heart rate reduction with ivabradine in two models of endothelial dysfunction and oxidative stress.
AU - Kröller-Schön, Swenja
AU - Schulz, Eberhard
AU - Wenzel, Philip
AU - Kleschyov, Andrei L
AU - Hortmann, Marcus
AU - Torzewski, Michael
AU - Oelze, Matthias
AU - Renné, Thomas
AU - Daiber, Andreas
AU - Münzel, Thomas
PY - 2011
Y1 - 2011
N2 - Heart rate reduction with the I(f)-channel-inhibitor ivabradine is a novel and appealing option in the therapy of patients with ischemic heart disease. The aim of the current study was to determine the effects of ivabradine in two different animal models of vascular disease characterized by increased oxidative stress and endothelial dysfunction. Wistar rats with angiotensin II induced hypertension and ApoE knockout mice were used as animal models of endothelial dysfunction and oxidative stress, with half of the animals receiving ivabradine 10 mg/kg/day in parallel. Ivabradine lead to a sustained 15-20% heart rate reduction, but had no effect on blood pressure. While ivabradine had no effect on endothelial function and vascular reactive oxygen species production in angiotensin II-treated rats, it improved both parameters in ApoE knockout mice. These antioxidative effects were associated with a decreased NADPH oxidase activity and the prevention of eNOS uncoupling. In addition, ivabradine treatment led 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.
AB - Heart rate reduction with the I(f)-channel-inhibitor ivabradine is a novel and appealing option in the therapy of patients with ischemic heart disease. The aim of the current study was to determine the effects of ivabradine in two different animal models of vascular disease characterized by increased oxidative stress and endothelial dysfunction. Wistar rats with angiotensin II induced hypertension and ApoE knockout mice were used as animal models of endothelial dysfunction and oxidative stress, with half of the animals receiving ivabradine 10 mg/kg/day in parallel. Ivabradine lead to a sustained 15-20% heart rate reduction, but had no effect on blood pressure. While ivabradine had no effect on endothelial function and vascular reactive oxygen species production in angiotensin II-treated rats, it improved both parameters in ApoE knockout mice. These antioxidative effects were associated with a decreased NADPH oxidase activity and the prevention of eNOS uncoupling. In addition, ivabradine treatment led 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.
KW - Animals
KW - Humans
KW - Male
KW - Disease Models, Animal
KW - Mice
KW - Mice, Knockout
KW - Chromatography, High Pressure Liquid
KW - Rats
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Immunoblotting
KW - Rats, Wistar
KW - Real-Time Polymerase Chain Reaction
KW - Heart Rate/drug effects
KW - Apolipoproteins E/deficiency
KW - Atherosclerosis/metabolism/physiopathology
KW - Benzazepines/pharmacology
KW - Endothelium, Vascular/drug effects/metabolism/physiopathology
KW - Hemodynamics/drug effects
KW - Hypertension/metabolism/physiopathology
KW - Luminescence
KW - Neutrophils
KW - Oxidative Stress/drug effects
KW - Reactive Oxygen Species
KW - Animals
KW - Humans
KW - Male
KW - Disease Models, Animal
KW - Mice
KW - Mice, Knockout
KW - Chromatography, High Pressure Liquid
KW - Rats
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Immunoblotting
KW - Rats, Wistar
KW - Real-Time Polymerase Chain Reaction
KW - Heart Rate/drug effects
KW - Apolipoproteins E/deficiency
KW - Atherosclerosis/metabolism/physiopathology
KW - Benzazepines/pharmacology
KW - Endothelium, Vascular/drug effects/metabolism/physiopathology
KW - Hemodynamics/drug effects
KW - Hypertension/metabolism/physiopathology
KW - Luminescence
KW - Neutrophils
KW - Oxidative Stress/drug effects
KW - Reactive Oxygen Species
M3 - SCORING: Journal article
VL - 106
SP - 1147
EP - 1158
JO - BASIC RES CARDIOL
JF - BASIC RES CARDIOL
SN - 0300-8428
IS - 6
M1 - 6
ER -
