Transient improvement of acetylcholine responses after short-term oral L-arginine in forearms of human heart failure

Patients with heart failure exhibit impaired endothelium-dependent vasodila tion. Although brief intraarterial administration of L-arginine improves en dothelium-dependent vasodilatation in these patients, long-term oral supple mentation is ineffective. To resolve these conflicting findings, we examine d the effect of a single, short-term oral dose of L-arginine on serial, hou rly forearm vascular responses to acetylcholine, sodium nitroprusside, and norepinephrine. Eighteen patients with heart failure were randomly allocate d in a double-blinded, crossover study to receive either a single 20-g oral dose of L-arginine or placebo, Vascular responses were measured by forearm venous occlusion plethysmography before and at 60, 120, and 180 min after dosage. Blood was obtained for measurement of L-arginine and nitric oxide m etabolite levels. Oral L-arginine increased plasma levels by fourfold at 60 , 120, and 180 min. Vasodilatation to acetylcholine. 37 mu g/min. was signi ficantly enhanced at 60 min (percentage increase in forearm blood flow: pla cebo, 413 +/- 64%: L-arginine, 587 +/- 94%; p < 0.05), discernible at 120 m in (p = 0.058) but no longer apparent at 180 min. Neither basal forearm blo od flow, sodium nitroprusside, nor norepinephrine responses nor plasma leve ls of nitrite and nitrate were altered. We conclude that although short-ter m oral supplementation with L-arginine produced marked sustained elevation of plasma levels of L-arginine in patients with heart failure, responses to acetylcholine were only transiently improved.