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 supplementati on of L-arginine on endothelium-dependent vasodilation in patients wit h congestive heart failure. Background. Endothelial dysfunction, as ev idenced by a 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 a semiessential amino acid, we investigated the effects of dietary L-arginine on endothelium dependent vasodilation in these patients.Me thods. Twenty patients with heart failure (New York Heart Association functional class III/IV, mean [+/-SE] age 51.3 +/- 1.7 years) and seve n healthy control subjects (mean age 52.6 +/- 3.3 years) were studied, All patients continued taking their usual treatment. Responses to ace tylcholine and sodium nitroprusside were determined using forearm plet hysmography. Patients with heart failure received either L-arginine (2 0 g/day every day for 28 days) or placebo (vehicle syrup in equal amou nts) in a double-blind protocol. The calculated power of the study was between 62% and 80% to detect a 30% to 40% change in area under the d ose-response (forearm vascular resistance) curve. Results. Responses t o acetylcholine, but not to sodium nitroprusside, were significantly a ttenuated in patients with heart failure compared with control subject s (mean area under curve [AUC], control subjects vs. patients with hea rt failure: 1,125.4 +/- 164.5 vs. 617.3 +/- 116.6 U, p < 0.05, by Stud ent t test), A significant increase in urea 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 aff ected by either L-arginine or placebo. Conclusions. Endothelial dysfun ction was apparent in patients with heart failure despite rigorous vas oactive treatment. Oral administration with L-arginine was ineffective in influencing endothelial function in these patients.