Effect of angiotensin-converting enzyme inhibitors on the peripheral circulation in heart failure

Abstract

In patients with chronic heart failure, the increase in blood flow to working muscle is attenuated and oxygen consumption is lower for any given workload of exercise, compared with normal subjects. This impaired metabolic vasodilation during exercise cannot be restored with short-term administration of angiotensin-converting enzyme (ACE) inhibitors. However, long-term ACE inhibition increases blood flow to skeletal muscle, and this increase is closely correlated with improvement in systemic oxygen consumption. The delayed effect of ACE inhibitors may be related to an interference with the vascular tissue renin-angiotensin system and remodeling of the vascular wall. In addition, endothelial-dependent dilation in response to acetylcholine is blunted in the forearm of patients with chronic heart failure, indicating an impaired endothelial function in this setting. There is experimental evidence that long-term ACE inhibition improves endothelial dysfunction; thus, one might speculate that the beneficial long-term effect of ACE inhibitors on peripheral flow may be, in part, related to its ability to restore normal endothelial function. Vasodilators such as hydralazinethat improve blood flow to working muscle after acute administration do not increase skeletal muscle oxygen consumption, indicating that oxygen utilization is not improved. Ultrastructural analysis of skeletal muscle revealed that intrinsic alterations of skeletal muscle exist in patients with chronic heart failure; that is, the oxidatrve capacity of skeletal muscle is impaired in severe heart failure and contributes to the reduced exercise capacity. Evaluation of skeletal muscle biopsies before and after long-term ACE inhibition revealed that the oxidative capacity of skeletal muscle can be increased after long-term therapy, thereby partially reversing the intrinsic alterations of working muscle in patients with chronic heart failure. It is concluded that the beneficial effect of ACE inhibitors is related, in part, to peripheral mechanisms (i.e., the ability of the peripheral vessels to dilate) and by improving peripheral oxygen utilization.