Peripheral vascular remodeling in patients with chronic heart failure

外周血管张力升高是慢性充血性心力衰竭（CHF）临床阶段和症状恶化的关键因素，原因是心脏后负荷增加和营养骨骼肌血流量减少。我们发现，根据纽约心脏协会分级（参考文献4和6），以一氧化氮（NO）生成为代表的内皮功能随着CHF临床严重程度的进展而显著衰减。这种内皮功能障碍出现在CHF的早期阶段。在病情的晚期，四肢阻力血管中的内皮依赖型和内皮非依赖型扩张机制都受到损害。这是因为血管内皮功能，尤其是NO的产生，是调节血管舒张功能的重要因素，对血管结构也有重要贡献。此外，尽管血管舒张循环因子如利钠多肽和新发现的肾上腺髓质素在心力衰竭中增加，但这些多肽激素在肢体血管床中的血管舒张效力明显减弱（参考文献5）。这些观察结果表明，CHF的外周循环衰竭不仅是由于简单的动脉肌肉收缩，而且是由于结构和功能的改变，包括血管中的受体和受体后水平。这种血管重构可能是肢体导管和骨骼肌内血管舒张衰竭的重要机制，并可能导致心力衰竭患者的左心室功能障碍和运动不耐受（Ref 1）。

Increased peripheral vascular tone is a critical factor in the deterioration of clinical stage and symptoms in chronic congestive heart failure (CHF) due to increased cardiac afterload and decreased nutritive skeletal muscle blood flow. We have found that 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 (Ref 4 and 6). 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, and 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 vasodilatory circulating factors such as natriuretic polypeptides and newly discovered adrenomedullin have been reported to be increased in heart failure, the vasodilatory potency of these polypeptide hormones in the limb vascular bed is significantly blunted (Ref. 5). These observations suggest that peripheral circulatory failure in CHF is due not only to simple arterial muscle constriction but also to structural and functional changes, including receptor and post-receptor levels in the vasculature. This vascular remodeling may be an important mechanism urderlying vasodilatory failure in both limb conduit and intra-skeletal muscle vessels, and may contribute significantly to left ventricular dysfunction and exercise intolerance in patients with heart failure (Ref 1).