Endothelial Function In Chronic Heart Failure Research Articles

Unending debate: Statin dilemma in the management of heart failure

In their recently published article Erbs et al. aimed to evaluate the pleiotropic effects of rosuvastatin on vascular and tissue regeneration, its impact on endothelial function and hemodynamics in 42 patients with chronic heart failure (CHF) [ [1] Erbs S. Beck E.B. Linke A. Adams V. Gielen S. Kränkel N. et al. High-dose rosuvastatin in chronic heart failure promotes vasculogenesis, corrects endothelial function, and improves cardiac remodeling — results from a randomized, double-blind, and placebo-controlled study. Int J Cardiol. 2010 Mar 15; (Electronic publication ahead of print) PubMed Google Scholar ]. They found that rosuvastatin activates circulating progenitor cells (CPCs) that contribute to neovascularisation and to the enhancement of endothelial function in CHF. Also they demonstrated that rosuvastatin improved LV performance by partly correction of vascular abnormalities.

Sauna therapy increases nitric oxide production through increasing arterial endothelial, but not inducible, nitric oxide synthase in heart failure

Purpose: Recent studies demonstrated that vascular endothelial dysfunction is involved in pathophysiology of chronic heart failure (CHF), and is mainly due to the decreased nitric oxide (NO) production by the decreased endothelial NO synthase (eNOS) expression and the increased oxidative stress. We previously reported that sauna therapy, using far infrared-ray dry sauna at 60 degrees centigrade, improves hemodynamics, vascular endothelial and cardiac function and clinical symptoms in CHF. The purpose of this study is to investigate the mechanisms by which sauna therapy improves endothelial function. Methods: Male TO-2 cardiomyopathic hamsters were used and were treated daily by sauna in which their rectal temperature raised almost 1 degree centigrade as clinical setting. Immunohistochemistry, Western blotting, reverse transcription-polymerase chain reaction and Griess regent reaction assay were performed to assess aortic eNOS, inducible NO synthase (iNOS) and concentration of serum nitrate. Results: Both eNOS mRNA and protein expression in aortas of TO-2 decreased with age. Four-week sauna therapy significantly increased eNOS mRNA and protein expression about 2 folds compared with those without sauna, but not modulated iNOS protein expression. Serum nitrate concentrations were increased by 4-week sauna therapy compared with those without sauna. Conclusions: Repeated sauna therapy increases NO production by the upregulation of the decreased eNOS expression in cardiomyopathic hamsters with heart failure, suggesting the improvement of endothelial function in CHF.

From tissue wasting to cachexia: changes inperipheral blood flow and skeletal musculature

Chronic heart failure (CHF) is characterized by a limitation in exercise capacity caused by breathlessness and fatigue. There is substantial evidence to suggest that these symptoms are largely determined by abnormalities of peripheral blood flow and skeletal muscle function, as opposed to central haemodynamic disturbances. Muscle atrophy and loss of strength, decreased oxidative capacity and structural changes in the skeletal musculature have all been reported in CHF. Abnormalities in peripheral blood flow also predict reduced exercise capacity, particularly in patients with cardiac cachexia. Endothelial dysfunction is present in CHF, together with an increase in peripheral vasomotor tone. The factors that regulate endothelial function in CHF are complex and poorly understood. The present review addresses abnormalities in endothelial function, regional blood flow and skeletal muscle in CHF, and their contributions to tissue wasting and cachexia.

Improvement of endothelial dysfunction in experimental heart failure by chronic RAAS-blockade: ACE-inhibition or AT1-receptor blockade?

Chronic heart failure (CHF) is associated with endothelial dysfunction. Activation of the renin-angiotensin-aldosterone system (RAAS) is believed to be important in the deterioration of endothelial dysfunction in CHF through stimulation of oxidative stress. Whereas angiotensin-converting enzyme inhibitors (ACE-I) improve endothelial function in CHF, the effects of angiotensin II AT1-receptor blockers (ARB) are less well established. Therefore we compared the effects of the ACE-I lisinopril vs. the ARB candesartan on endothelial dysfunction in a rat model of CHF. CHF was induced by myocardial infarction (MI) after coronary ligation. Two weeks after MI, daily treatment with lisinopril (2 mg/kg) or candesartan cilexetil (1.5 mg/kg) was started. After 13 weeks, rats were sacrificed and endothelial function was determined by measuring acetylcholine (ACh)-induced vasodilation in aortic rings, with selective presence of the nitric oxide synthase (NOS)-inhibitor NG-monomethyl-L-arginine (L-NMMA) to determine the contribution of nitric oxide (NO). ACh-induced vasodilation was attenuated in untreated MI (-50%) compared with control rats. This was in part due to an impaired contribution of NO (-49%). Lisinopril and candesartan cilexetil fully normalised ACh-induced dilation, including the part mediated by NO. Chronic RAAS-blockade with lisinopril and candesartan cilexetil normalised endothelial function in CHF in a comparable way. The effect of both treatments included the increase of the NO-mediated dilation, further indicating the important role of oxidative stress in the relationship between the RAAS and endothelial dysfunction in CHF.