Peripheral vascular remodeling in chronic heart failure: Clinical relevance and new conceptualization of its mechanisms

Increased peripheral vascular tone is a critical factor in the deterioration of clinical stage and symptoms in chronic congestive heart failure (CHF) because of increased cardiac afterload and decreased nutritive skeletal muscle blood flow. Endothelial function as represented by nitric oxide (NO) production shows significant attenuation with the progression of clinical severity of CHF as determined by New York Heart Association class and exercise capacity parameters. This endothelial dysfunction emerges in the early stages of CHF. In the advanced stage of the condition, both endothelium-dependent and endothelium-independent dilator mechanisms are impaired in limb resistance vessels. This occurs because vascular endothelial function, especially NO production, is an important factor in the regulation of vasodilatory function, as well as making an important contribution to vascular structure. Furthermore, although such vasodilatory circulating factors as natriuretic polypeptides and newly discovered adrenomedullin are increased in heart failure, the vasodilatory potency of these polypeptide hormones in the limb vascular bed is significantly blunted. These observations suggest that peripheral circulatory failure in CHF is caused not only by simple arterial muscle constriction, but also by structural and functional changes, including receptor and postreceptor levels in the vasculature. This vascular remodeling may be an important mechanism underlying vasodilatory failure in both limb conduit and intraskeletal muscle vessels and may contribute significantly to left ventricular dysfunction and exercise intolerance in patients with heart failure.