Effect of angiotensin-converting enzyme inhibitors on endothelium-dependent peripheral vasodilation in patients with chronic heart failure

Second Department of Internal Medicine, Iwate Medical University, Morioka, Japan.

OBJECTIVES: This study was performed to determine whether acute inhibition of angiotensin-converting enzyme restores impaired endothelium-dependent vasorelaxation in patients with chronic heart failure. BACKGROUND. Recent reports have demonstrated that endothelium-dependent vasodilation induced by cholinergic stimuli is attenuated in the peripheral vascular bed of patients with chronic heart failure. METHODS. We examined the effects of local intraarterial infusion of enalaprilat (0.6 micrograms/min per 100 ml tissue volume) on responses initiated by acetylcholine or sodium nitroprusside in the forearm vascular bed in 8 normal subjects, 12 patients with mild heart failure (New York Heart Association functional classes I and II) and 10 patients with more advanced heart failure (functional classes III and IV). Forearm blood flow was measured by means of venous occlusion plethysmography. RESULTS. Although enalaprilat alone did not affect basal forearm blood flow, it significantly augmented the increase in forearm blood flow induced by acetylcholine in normal subjects (p < 0.01) and in those with mild heart failure (p < 0.05). However, the effect was not found in patients with more advanced heart failure. Coinfusion of enalaprilat did not enhance sodium nitroprusside-induced vasodilation in any of the groups. To explore the mechanism of the inhibitor's effect, an additional 20 patients with mild heart failure (functional class II) were pretreated with a cyclooxygenase inhibitor, acetylsalicylic acid (n = 10) or an inhibitor of nitric oxide synthesis, NG-monomethyl-L-arginine (n = 10), followed by administration of acetylcholine with or without enalaprilat. Acetylsalicylic acid reduced the converting enzyme inhibitor's effect, whereas NG-monomethyl-L-arginine failed to block the augmentation of blood flow. CONCLUSIONS. These results suggest that inhibition of angiotensin-converting enzyme potentiates endothelium-dependent vasodilation induced by cholinergic stimuli, presumably through modulation of prostaglandin metabolism, in the peripheral vasculature of patients with mild chronic heart failure.

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