Strong evidence exists that reduced vascular reactivity is present in patients with heart failure, and that vascular function affects exercise capacity. The proposed studies will test the hypothesis that, in heart failure, intensive medical therapy and exercise training improve exercise- induced vascular reactivity by increasing bioavailability of endothelium- derived nitric oxide. First, the calf blood flow response to acetylcholine (an endothelium-dependent vasodilator), NG-monomethyl-L-arginine (a nitric oxide synthase inhibitor), and nitroprusside (an endothelium-independent vasodilator) will be determined at rest and during isotonic exercise by venous occlusion plethysmography in heart failure patients. Second, oxygen uptake kinetics during sub-maximal and maximal leg exercise testing will be measured with breath-by-breath gas analysis and correlated with the leg vascular response to the above =-mentioned pharmacologic interventions. Finally, changes in leg blood flow response to acetylcholine, Ng- monomethyl-L-arginine, and nitroprusside will be determined before and after twelve weeks of leg exercise conditioning. These studies will lead to a greater understanding of clinically important vasomotor abnormalities in heart failure, and will determine th e potential for improvement in funcTIonal capacity after correction of vascular dysfunction.
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