Peripheral vascular remodeling in patients with chronic heart failure

由于心脏后负荷增加和营养性骨骼肌血流量减少，外周血管张力增加是慢性充血性心力衰竭（CHF）临床分期和症状恶化的关键因素。我们已经发现，由一氧化氮（NO）产生所代表的内皮功能随着由纽约心脏协会分级确定的CHF临床严重程度的进展而显示出显著的衰减（参考文献4和6）。这种内皮功能障碍出现在CHF的早期阶段。在病情的晚期阶段，在肢体阻力血管中，内皮依赖性和内皮非依赖性扩张机制均受损。发生这种情况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，并对血管结构做出重要贡献。此外，尽管有报告称心力衰竭时血管舒张循环因子（如利钠多肽和新发现的肾上腺髓质素）增加，但这些多肽激素在肢体血管床中的血管舒张效力显著减弱（参考文献5）。这些观察结果表明，CHF外周循环衰竭不仅是由于简单的动脉肌肉收缩，而且结构和功能的变化，包括受体和受体后血管水平。这种血管重塑可能是导致肢体管道和骨骼肌内血管舒张功能衰竭的重要机制，并可能显著导致心力衰竭患者的左心室功能障碍和运动不耐受（参考文献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).