Dietary supplementation with l-arginine fails to restore endothelial function in forearm resistance arteries of patients with severe heart failure

Objectives. We sought to examine the efficacy of dietary supplementation of l-arginine on endothelium-dependent vasodilation in patients with congestive heart failure. Background. Endothelial dysfunction, as evidenced by diminished response to such vasodilators as acetylcholine, is well defined in patients with heart failure. These responses are improved by intraarterial infusion with l-arginine. Because l-arginine is semiessential amino acid, we investigated the effects of dietary l-arginine on endothelium-dependent vasodilation in these patients. Methods. Twenty patients with heart failure (New York Heart Association functional class III/IV, mean [±SE] age 51.3 ± 1.7 years) and seven healthy control subjects (mean age 52.6 ± 3.3 years) were studied. All patients continued taking their usual treatment. Responses to acetylcholine and sodium nitroprusside were determined using forearm plethysmography. Patients with heart failure received either l-arginine (20 g/day every day for 28 days) or placebo (vehicle syrup in equal amounts) in double-blind protocol. The calculated power of the study was between 62% and 80% to detect 30% to 40% change in are under the dose-response (forearm vascular resistance) curve. Results. Responses to acetylcholine, but not to sodium nitroprusside, were significantly attenuated in patients with heart failure compared with control subjects (mean are under curve [Auc], control subjects vs. patients with heart failure: 1,125.4 ± 164.5 vs. 617.3 ± 116.6 U, p < 0.05, by Student t test). significant increase in ure and aspartate transaminase levels in patients receiving active l-arginine treatment was observed. Responses to acetylcholine (AUC; before vs. after l-arginine: 641.5 ± 126.7 vs. 695.9 ± 151.9 U) and sodium nitroprusside were not affected by either l-arginine or placebo. Conclusions. Endothelial dysfunction was apparent in patients with heart failure despite rigorous vasoactive treatment. Oral administration with l-arginine was ineffective in influencing endothelial function in these patients.