Ivabradine Ameliorates Cardiac Diastolic Dysfunction in Diabetic Mice Independent of Heart Rate Reduction

Heart rate reduction by ivabradine improves aortic compliance in apolipoprotein E-deficient mice.

BACKGROUND Impaired vascular compliance is associated with cardiovascular mortality. The effects of heart rate on vascular compliance are unclear. Therefore, we characterized effects of heart rate reduction (HRR) by I(f) current inhibition on aortic compliance and underlying molecular mechanisms in apolipoprotein E-deficient (ApoE(-)/(-)) mice. METHODS ApoE(-)/(-) mice fed a high-cholesterol ...

Effect of graded heart rate reduction with ivabradine on myocardial oxygen consumption and diastolic time in exercising dogs.

Lowering heart rate reduces myocardial oxygen consumption (MVO2) and produces potent anti-ischemic effects. The development of selective heart rate-reducing agents represents an alternative approach to the use of beta-blockers. Therefore, our goal was to establish the dose-response curve of the effects of ivabradine (If channel inhibitor) on MVO2 and diastolic time. Seven conscious and chronica...

Glycogen Synthase Kinase-3β Inhibition Ameliorates Cardiac Parasympathetic Dysfunction in Type 1 Diabetic Akita Mice

Decreased heart rate variability (HRV) is a major risk factor for sudden death and cardiovascular disease. We previously demonstrated that parasympathetic dysfunction in the heart of the Akita type 1 diabetic mouse was due to a decrease in the level of the sterol response element-binding protein (SREBP-1). Here we demonstrate that hyperactivity of glycogen synthase kinase-3β (GSK3β) in the atri...

Angiotensin 1-7 Ameliorates Diabetic Cardiomyopathy and Diastolic Dysfunction in db/db Mice by Reducing Lipotoxicity and Inflammation Mori et al: Angiotensin 1-7 Ameliorates Diabetic Cardiomyopathy

Heart Failure Uncoupled Cardiac Nitric Oxide Synthase Mediates Diastolic Dysfunction

Background—Heart failure with preserved ejection fraction is 1 consequence of hypertension and is caused by impaired cardiac diastolic relaxation. Nitric oxide (NO) is a known modulator of cardiac relaxation. Hypertension can lead to a reduction in vascular NO, in part because NO synthase (NOS) becomes uncoupled when oxidative depletion of its cofactor tetrahydrobiopterin (BH 4) occurs. Similar...