Drexler H, Münzel T, Riede U, Just H
Medizinische-Klinik III, University of Freiburg, Federal Republic of Germany.
Am J Cardiol. 1991 May 6;67(12):29C-34C; discussion 34C-35C. doi: 10.1016/0002-9149(91)90073-t.
Systemic vasoconstriction in chronic heart failure is due to several compensatory mechanisms with different time courses. Peripheral vasoconstriction mediated by increased sympathetic tone and activation of the plasma renin-angiotensin system may act primarily for short-term control. The effects of the vascular renin-angiotensin system, impaired flow-dependent, endothelium-mediated dilation (resulting from chronically reduced flow) and structural alterations of the vessel wall slowly emerge with time. In addition, fluid retention may contribute to increased vascular stiffness in chronic heart failure. Improved cardiac output with acute administration of vasodilators and inotropes is not immediately translated into increased blood flow to skeletal muscle, because (1) the reversal of the peripheral alterations described develops slowly over time (in fact, vasodilators and inotropes given acutely may cause redistribution of blood flow in skeletal muscle without improving oxygen availability); and (2) intrinsic abnormalities of skeletal muscle exist in chronic heart failure (e.g., due to chronic deconditioning, resulting in reduced oxidative capacity of skeletal muscle, as suggested by ultrastructural analysis and nuclear magnetic resonance spectroscopy). Drugs that interfere with the underlying compensatory mechanisms (e.g., renin-angiotensin system) without development of tolerance during long-term therapy exert beneficial effects after long-term treatment (e.g., the beneficial effects of angiotensin-converting enzyme inhibitors are, in part, due to peripheral mechanisms--the inability of the peripheral vessels to dilate--and to improvement of peripheral oxygen extraction).
慢性心力衰竭时的全身血管收缩是由几种具有不同时程的代偿机制引起的。由交感神经张力增加和血浆肾素-血管紧张素系统激活介导的外周血管收缩可能主要起短期控制作用。血管肾素-血管紧张素系统的作用、血流依赖性内皮介导舒张功能受损（由长期血流减少导致）以及血管壁结构改变会随着时间缓慢出现。此外，液体潴留可能导致慢性心力衰竭时血管僵硬度增加。急性给予血管扩张剂和正性肌力药物改善心输出量后，并不会立即转化为骨骼肌血流增加，原因如下：（1）上述外周改变的逆转随时间缓慢发生（事实上，急性给予血管扩张剂和正性肌力药物可能导致骨骼肌血流重新分布，而不改善氧供应）；（2）慢性心力衰竭时骨骼肌存在内在异常（例如，由于长期失用，导致骨骼肌氧化能力降低，超微结构分析和核磁共振波谱研究表明）。在长期治疗中不会产生耐受性且能干扰潜在代偿机制（如肾素-血管紧张素系统）的药物，在长期治疗后会发挥有益作用（例如，血管紧张素转换酶抑制剂的有益作用部分归因于外周机制——外周血管无法扩张——以及外周氧摄取的改善）。
