1: Is endothelium function impaired in COPD? Other chronic cardiovascular diseases are associated with endothelial dysfunction, and the endothelium plays an important role in regulating vascular tone, tissue blood flow, coagulation and the inflammation process. Although the specific causes of endothelial dysfunction remain unclear, physical inactivity, chronic systemic inflammation and smoking are all known to be associated with endothelial abnormality.

2. Is Muscular Sympathetic Nerve Activity (MSNA) increased in COPD? A balanced regulation of blood flow to skeletal muscles may be disturbed by pathophysiology and may therefore contribute to the exercise intolerance and skeletal muscle depletion seen in patients with COPD.Skeletal muscle blood flow is tightly regulated to match tissue oxygen demands and is thus adapted to meet energy requirements. During physical activity, the sympathetic nervous system is activated ("exercise pressor reflex"), resulting in increased ventilation, heart rate and a redistribution of cardiac output from inactive to active tissues. The redistribution of cardiac output to the body organs is heterogeneous. Blood flow to skeletal, respiratory and cardiac muscle increases as exercise intensity increases, whereas blood flow to gastrointestinal, renal and reproductive tissues decreases. As blood pressure during exercise remains largely unchanged, the redistribution of blood flow is caused by changes in vascular conductance. These conductance changes are caused by an overall vasoconstriction induced by the increased sympathetic outflow of noradrenaline (NA), and a vasodilation of vascular beds supplying the working skeletal -, cardiac- and respiratory muscle.

Inclusion Criteria:

• Forced Expiratory Volume at on second/ Forced Vital Capacity fixed ratio <0.70, - Forced Expiratory Volume at one second <60% of predicted and Medical
• Research Council scale > or equal to 3
• Arterial oxygen saturation at rest> 90%,
• Body Mass Index >18,
• Left Ventricle Ejection Fraction> 45.

Exclusion Criteria:

• Unstable ischemic heart disease,
• severe heart valve failure,
• pulmonary emboli,
• severe heart failure,
• severe infections,
• musculoskeletal disorders,
• malignant disease,
• contraindicated medicine as anticoagulants.