VASCULAR AND HORMONAL RESPONSES TO ARGININE - PROVISION OF SUBSTRATE FOR NITRIC-OXIDE OR NONSPECIFIC EFFECT

1. The vascular and hormonal effects of L- and D-arginine were compared in healthy subjects and in patients with insulin-dependent diabetes mellitus or untreated essential hypertension. 2. Infusion of L- or D-arginine (40 mu mol/l) in the forearm vascular bed, sufficient to increase the local concentration approximately 20-fold, had no effect on blood flow or the vasodilator response to acetylcholine (30 and 100 nmol/min) in patients with insulin-dependent diabetes (n=7) or essential hypertension (n=7), or in age- and sex-matched control subjects (n=7 in both groups). 3. Systemic infusion of 10g of L-arginine (n=5) or D-arginine (n=3) increased plasma concentration of arginine approximately 20-fold without altering supine or erect haemodynamics, Increases in plasma insulin, prolactin and glucagon were seen with both enantiomers. The stereopurity of arginine was confirmed in a cell-culture assay system. 4. We conclude that, in healthy subjects and patients with essential hypertension or insulin-dependent diabetes, synthesis of nitric oxide within the vasculature is not limited by substrate availability. At high concentrations of arginine, non-stereospecific effects, including alterations in hormone concentration, occur. It remains to be determined whether these nonstereospecific hormonal changes might contribute to certain haemodynamic effects of arginine.