Peripheral vascular remodeling in patients with chronic heart failure

慢性充血性心力衰竭(CHF)患者由于心脏后负荷增加，营养骨骼肌血流量减少，导致外周血管张力增加，是临床分期和症状恶化的重要因素。我们发现，以一氧化氮(NO)产生为代表的内皮功能随着纽约心脏协会分级的CHF临床严重程度的进展而显著减弱(参考文献4和6)。这种内皮功能障碍出现在CHF的早期阶段，在疾病的晚期，肢体阻力血管的内皮依赖性和非内皮依赖性扩张器机制都受到损害。这是因为血管内皮功能，特别是NO的产生，是调节血管扩张功能的一个重要因素，也是对血管结构做出重要贡献的一个因素。此外，尽管如利钠多肽和新发现的肾上腺髓质素等血管扩张循环因子已被报道在心力衰竭中增加，但这些多肽激素在肢体血管床中的血管扩张效力明显减弱(参考文献)。5)。这些观察表明，CHF患者的外周循环衰竭不仅是由于单纯的动脉肌肉收缩，而且是由于结构和功能的变化，包括血管系统中受体和受体后水平的变化。这种血管重构可能是导致肢体管道和骨骼肌内血管舒缩功能衰竭的重要机制，并可能导致心力衰竭患者的左心功能不全和运动耐量增加(文献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).