In human heart failure (HF), reduced cardiac function has, at least partly, been ascribed to altered calcium homeostasis in cardiomyocytes. The effects of the calcium sensitizer levosimendan on diastolic dysfunction caused by reduced removal of calcium from cytosol in early diastole are not well known. In this study, we investigated the effect of long-term levosimendan treatment in a murine mod...

Adult offspring of severely diabetic pregnant rats are insulin resistant and display cardiovascular dysfunction. When pregnant they develop mild hyperglycaemia. Diets high in saturated fat have been implicated in the development of cardiovascular disease and vascular dysfunction. In the present study we have determined vascular function in small mesenteric arteries from offspring of normal (OC)...

Reactive oxygen species play a central role in vascular inflammation and atherogenesis, with enhanced superoxide (O2.-) production contributing significantly to impairment of nitric oxide (.NO)-dependent relaxation of vessels from cholesterol-fed rabbits. We investigated potential sources of O2.- production, which contribute to this loss of endothelium-dependent vascular responses. The vasorela...

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...

Hyperhomocysteinemia is a risk factor for stroke, myocardial infarction, and venous thrombosis. Moderate hyperhomocysteinemia is associated with impaired endothelial function, but the mechanisms responsible for endothelial dysfunction in hyperhomocysteinemia are poorly understood. We have used genetic and dietary approaches to produce hyperhomocysteinemia in mice. Heterozygous cystathionine bet...

OBJECTIVE In mice that are heterozygous for mitochondrial superoxide dismutase (SOD2(+/-)) with apoE deficiency (apoE(-/-)), mitochondrial DNA damage increases formation of atherosclerotic lesions. The purpose of this study was to determine whether SOD2 provides protection against increased vascular superoxide and endothelial dysfunction in apoE-deficient mice. METHODS AND RESULTS Four groups...

BACKGROUND Through ventricular interdependence, pulmonary hypertension (PH) induces left ventricular (LV) dysfunction. We hypothesized that pediatric PH patients have LV diastolic dysfunction, related to adverse pulmonary hemodynamics, leftward septal shift, and prolonged right ventricular systole. METHODS AND RESULTS Echocardiography was prospectively performed at 2 institutions in 54 pediat...