Restoring vascular nitric oxide formation by L-arginine improves the symptoms of intermittent claudication in patients with peripheral arterial occlusive disease

Background. Administration of L-arginine improves nitric oxide (NO) formation and endothelium dependent vasodilation in atherosclerotic patients. Objectives. We investigated in this double blind, controlled study whether prolonged intermittent infusion therapy with L-arginine improves the clinical symptoms of patients with intermittent claudication, as compared with the endothelium independent vasodilator prostaglandin E-1, and control patients. Methods. Thirty-nine patients with intermittent claudication were randomly assigned to receive 2 x 8 g L-arginine/day, or 2 x 40 mu g prostaglandin E-1 (PGE(1))/day or no hemodynamically active treatment, for 3 weeks. The pain-free and absolute walking distances were assessed on a walking treadmill at 3 km/h, 12% slope, and NO-mediated, flow induced vasodilation of the femoral artery was assessed by ultrasonography at baseline, at 1, 2 and 3 weeks of therapy and 6 weeks after the end of treatment. Urinary nitrate and cyclic guanosine-3', 5'-monophosphate (GMP) were assessed as indices of endogenous NO production. Results. L-Arginine improved the pain-free walking distance by 230 +/- 63% and the absolute walking distance by 155 +/- 48% (each p < 0.05). Prostaglandin E-1 improved both parameters by 209 +/- 63% and 144 +/- 28%, respectively (each p < 0.05), whereas control patients experienced no significant change. L-Arginine therapy also improved endothelium-dependent vasodilation in the femoral artery, whereas PGE, had no such effect, There was a significant linear correlation between the L arginine/asymmetric dimethyl-arginine (ADMA) ratio and the pain free walking distance at baseline (r = 0.359, p < 0.03). L-Arginine treatment elevated the plasma L-Arginine/ADMA ratio and increased urinary nitrate and cyclic GMP excretion rates, indicating normalized endogenous NO formation. Prostaglandin E-1 therapy had no significant effect on any of these parameters. Symptom scores assessed on a visual analog scale Increased from 3.51 +/- 0.18 to 8.3 +/- 0.4 (L-arginine) and 7.0 +/- 0.5 (PGE(1); each p < 0.05), but did not significantly change in the control group (4.3 +/- 0.4). Conclusions. Restoring NO formation and endothelium-dependent vasodilation by L arginine improves the clinical symptoms of intermittent claudication in patients with peripheral arterial occlusive disease. (C) 1998 by the American College of Cardiology.