L-ARGININE INDUCES NITRIC OXIDE-DEPENDENT VASODILATION IN PATIENTS WITH CRITICAL LIMB ISCHEMIA - A RANDOMIZED, CONTROLLED-STUDY

Background L-Arginine is the precursor of endogenous nitric oxide (NO) , which is a potent vasodilator acting via the intracellular second-me ssenger cGMP. In healthy humans, L-arginine induces peripheral vasodil ation and inhibits platelet aggregation due to an increased NO product ion. Prostaglandin E(1) (PGE(1)) induces peripheral vasodilation via s timulating prostacyclin receptors. Methods and Results We investigated the effects of one intravenous infusion of L-arginine (30 g, 60 minut es) or PGE(1) (40 mu g, 60 minutes) versus those of placebo (150 mL 0. 9% saline, 60 minutes) on blood pressure, peripheral hemodynamics, and urinary NO3- and cGMP excretion rates in patients with critical limb ischemia (peripheral arterial occlusive disease stages Fontaine III or IV). Blood flow in the femoral artery was significantly increased by L-arginine (+ 42.3 +/- 7.9%, P < .05) and by PGE(1) (+ 31.0 +/- 10.2%, P < .05) but not by placebo (+ 4.3 +/- 13.0%, P = NS). Urinary NO3- e xcretion increased by 131.8 +/- 39.5% after L-arginine (P < .05) but o nly by 32.3 +/- 17.2% after PGE(1) (P = NS). Urinary cGMP excretion in creased by 198.7 +/- 84.9% after L-arginine (P < .05) and by 94.2 +/- 55.8% after PGE(1) (P = NS). Both urinary index metabolites were uncha nged by placebo. Conclusions We conclude that intravenous L-arginine i nduces NO-dependent peripheral vasodilation in patients with critical limb ischemia. These effects are paralleled by increased urinary NO3- and cGMP excretion, indicating an enhanced systemic NO production. Inc reased urinary NO3- excretion may be a sum effect of NO synthase subst rate provision (L-arginine) and increased shear stress (PGE(1) and L-a rginine).