Dose-related effect of intravenous L-arginine on muscular blood flow of the calf in patients with peripheral vascular disease: a H2I5O

1. Endothelium-derived nitric oxide (NO) contributes to the regulation of vascular tone and blood pressure. Infusion of L-arginine produces systemic vasodilatation via stimulation of endogenous NO formation. Vasodilatation is accompanied by an increase in peripheral arterial blood flow. However, it is not known whether capillary nutritive blood flow increases as well. The time course and doseresponse pattern of this effect remain to be elucidated. 2. ltivo groups of ten patients with peripheral vascular disease (PVD) received an intravenous infusion of 8 g or 30 g of L-arginine over a period of 40 min. Blood pressure and heart rate were monitored noninvasively. Muscular blood flow (MBF) of the calf was determined at 0, 20, 40, 60, 80 min by positron emission tomography with Hz150 as flow tracer. Plasma L-arginine and cyclic GMP (cGMP) levels were determined at the same time points. 3. L-arginine induced a dose-related decrease in blood pressure during the infusion period. MBF and plasma cGMP levels during and after the infusion of 8 g of L-arginine did not change significantly. In the patients receiving 30g of L-arginine, MBF was enhanced significantly from 1.56 & 0.14 to 2.09f0.21 ml min-l 100 ml-l a t 40 min and 2.23f0.15 ml min-' 100 ml-l after 80 rnin (+43.0%). The increase in MBF was paralleled by an increase in plasma cGMP from 4789.8k392.2 nmol/l a t baseline to 9223.2f1233.6 nmol/l at 40 min. 4. We conclude that intravenous L-arginine enhances nutritive capillary MBF in patients with PVD via the NO-cGMP pathway in a dose-related manner. This effect might be therapeutically beneficial in patients with PVD. INTRODUCTION