MECHANISMS AND IMPLICATIONS OF ENDOTHELIAL DYSFUNCTION IN CONGESTIVE-HEART-FAILURE

The pathogenesis of heart failure is determined by the ventricular and vascular responses to myocellular injury. Experimental and clinical s tudies suggest that the vascular endothelium may play an important rol e in modulating progression of ventricular and vascular remodeling in heart failure. Endothelial cell dysfunction has been described in the coronary and skeletal muscle circulations of patients with heart failu re and appears to be characterized by decreased endothelial synthesis of nitric oxide and increased production of endothelin-l. The pathogen esis of endothelial dysfunction in hear? failure is unknown, but may b e related to increased oxidative stress, abnormal regional flow condit ions, and cytokine and neurohormonal activation. The specific role of endothelial dysfunction in the pathogenesis of heart failure remains t o be determined. If endothelial dysfunction does contribute to progres sion of disease in early heart failure, specific therapies to enhance endothelial dysfunction may improve long-term morbidity and mortality.