EFFECT OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS ON ENDOTHELIUM-DEPENDENT PERIPHERAL VASODILATION IN PATIENTS WITH CHRONIC HEART-FAILURE

Objectives. This study was performed to determine whether acute inhibi tion of angiotensin-converting enzyme restores impaired endothelium de pendent vasorelaxation in patients with chronic heart failure. Backgro und. Recent reports have demonstrated that endothelium-dependent vasod ilation induced by cholinergic stimuli is attenuated in the peripheral vascular bed of patients with chronic heart failure. Methods. We exam ined the effects of local intraarterial infusion of enalaprilat (0.6 m u g/min per 100 ml tissue volume) on responses initiated by acetylchol ine or sodium nitroprusside in the forearm vascular bed in 8 normal su bjects, 12 patients with mild heart failure (New York Heart Associatio n functional classes I and II) and 10 patients with more advanced hear t failure (functional classes III and IV). Forearm blood flow was meas ured by means of venous occlusion plethysmography. Results. Although e nalaprilat alone did not affect basal forearm blood flow, it significa ntly augmented the increase in forearm blood flow induced by acetylcho line in normal subjects (p < 0.01) and in those with mild heart failur e (p < 0.05). However, the effect was not found in patients with more advanced heart failure. Coinfusion of enalaprilat did not enhance sodi um nitroprusside-induced vasodilation in any of the groups. To explore the mechanism of the inhibitor's effect, an additional 20 patients wi th mild heart failure (functional class II) were pretreated with a cyc looxygenase inhibitor, acetylsalicylic acid (n = 10) or an inhibitor o f nitric oxide synthesis, N-G-monomethyl L-arginine (n = 10), followed by administration of acetylcholine with or without enalaprilat. Acety lsalicylic acid reduced the converting enzyme inhibitor's effect, wher eas N-G-monomethyl-L-arginine failed to block the augmentation of bloo d flow.Conclusions. These results suggest that inhibition of angiotens in-converting enzyme potentiates endothelium-dependent vasodilation in duced by cholinergic stimuli, presumably through modulation of prostag landin metabolism, in the peripheral vasculature of patients with mild chronic heart failure.