Quantifying the l-arginine paradox in vivo

NO and PO2 microelectrodes were used to quantify the effects of increased availability of l-arginine in an exteriorized rat mesentery and small intestine microcirculatory preparation in n = 16 rats. During short periods of elevated l-arginine added to the superfusion bath, transient changes in perivascular NO or PO2 were measured at 171 perivascular sites near intestinal arterioles and venules, simultaneously with tissue perfusion using laser Doppler flowmetry (LDF). Excess l-arginine increased perivascular NO over twofold, by 411 ± 42 nM above the baseline of 329 ± 30 nM (P < 0.0001), and increased tissue perfusion by 35.5 ± 7.5% (P < 0.0001). No difference between arterioles and venules was observed in the magnitude or time course of the NO responses. Both increases and decreases in perivascular PO2 were observed after excess l-arginine, with a similar increase in tissue perfusion by 42.0 ± 12.3% (P < 0.0001). Our NO measurements confirm that increased bioavailability of l-arginine causes a significant increase in NO production throughout the microcirculation of this preparation, with increased tissue perfusion, and provides direct in vivo evidence for the l-arginine paradox.