Is l-arginine infusion an adequate tool to assess endothelium-dependent vasodilation of the human renal vasculature?

Abstract

Systemic administration of L-arginine alters renal haemodynamics in humans. We examined whether L-arginine-induced vasodilation of the renal vasculature is related to an increased production and release of NO by comparing the effects of L- and D-arginine on renal endothelium-dependent vasodilation. In a double-blind randomized cross-over study including 20 young, healthy male white subjects (age 26+/-2 years), we determined the effects of intravenous administration of L-arginine or its enantiomer D-arginine, at doses of 100 mg/kg body weight for 30 min or 500 mg/kg for 30 min, on renal haemodynamics. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were assessed by a constant-infusion input-clearance technique (using p-aminohippuric acid and inulin respectively). In addition, changes in blood pressure, heart rate, urinary sodium excretion (U(Na)) and urinary cGMP were measured. HPLC was used to determine L- and D-arginine concentrations. Intravenous infusion of L-arginine at 100 mg/kg for 30 min increased RPF from 641+/-87 to 677+/-98 ml/min (P=0.019), whereas infusion of D-arginine did not (from 642+/-74 to 657+/-86 ml/min; not significant). The change in RPF was more marked during the infusion of L-arginine than during the infusion of D-arginine (+36+/-61 versus +16+/-57 ml/min; P=0.037). Infusion of both L- and D-arginine at doses of 500 mg/kg for 30 min increased RPF from baseline [from 641+/-87 to 762+/-133 ml/min (P<0.001) and from 642+/-74 to 713+/-120 ml/min (P=0.004) respectively], but the change in RPF again was greater in response to L-arginine infusion than to infusion with D-arginine (+121+/-97 versus +71+/-94 ml/min; P=0.018). In accordance, changes in renal vascular resistance (RVR) were higher in response to L-arginine compared with D-arginine for both doses (P<0.05 and P<0.001 respectively). U(Na) increased only with L-arginine (change in U(Na), +0.33+/-0.26 mmol/min; P<0.01) but not with D-arginine (change in U(Na), +0.11+/-0.17 mmol/min; not significant). The change in U(Na) was more pronounced during infusion of L-arginine compared with infusion of D-arginine (P=0.023). In parallel, urinary excretion of cGMP only increased in response to L-arginine (+676+/-272 pmol/l; P=0.038) and not during D-arginine infusion (+185+/-153 pmol/l; not significant). L-Arginine-induced changes in RPF, RVR, U(Na) and cGMP excretion differed significantly from those induced by D-arginine. Thus although no direct measurements of NO synthesis were performed, putative markers of NO synthesis suggest that the renal vasodilatory response to L-arginine, at least in part, was due to increased production and release of NO. The dose of L-arginine at 100 mg/kg for 30 min emerged as the most suitable, because of the absence of systemic haemodynamic changes. The effects of infusion of L-arginine at 500 mg/kg for 30 min on renal endothelium-dependent vasodilation need to be corrected for the effects of D-arginine before conclusions can be drawn.