DOSE-RELATED EFFECT OF INTRAVENOUS L-ARGININE ON MUSCULAR BLOOD-FLOW OF THE CALF IN PATIENTS WITH PERIPHERAL VASCULAR-DISEASE - A H-2 O-15 POSITRON EMISSION TOMOGRAPHY STUDY

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. Va sodilatation is accompanied by an increase in peripheral arterial bloo d flow. However, it is not known whether capillary nutritive blood flo w increases as well. The time course and dose-response pattern of this effect remain to be elucidated. 2. Two groups of ten patients with pe ripheral 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 he art rate were monitored noninvasively. Muscular blood how (MBF) of the calf was determined at 0, 20, 40, 60, 80 min by positron emission tom ography with (H2O)-O-15 as flow tracer. Plasma L-arginine and cyclic G MP (cGMP) levels were determined at the same time points. 3. L-arginin e induced a dose-related decrease in blood pressure during the infusio n period. MBF and plasma cGMP levels during and after the infusion of 8 g of L-arginine did not change significantly. In the patients receiv ing 30 g of L-arginine, MBF was enhanced significantly from 1.56 +/- 0 .14 to 2.09 +/- 0.21 ml min(-1) 100 ml(-1) at 40 min and 2.23 +/- 0.15 ml min(-1) 100 ml(-1) after 80 min (+ 43.0%). The increase in MBF was paralleled by an increase in plasma cGMP from 4789.8 +/- 392.2 nmol/l at baseline to 9223.2 +/- 1233.6 nmol/l at 40 min. 4. We conclude tha t 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.