l -Arginine Induces Nitric Oxide–Dependent Vasodilation in Patients With Critical Limb Ischemia

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Abstract
Background l -Arginine is the precursor of endogenous nitric oxide (NO), which is a potent vasodilator acting via the intracellular second-messenger cGMP. In healthy humans, l -arginine induces peripheral vasodilation and inhibits platelet aggregation due to an increased NO production. Prostaglandin E 1 (PGE 1 ) induces peripheral vasodilation via stimulating prostacyclin receptors. Methods and Results We investigated the effects of one intravenous infusion of l -arginine (30 g, 60 minutes) or PGE 1 (40 μg, 60 minutes) versus those of placebo (150 mL 0.9% saline, 60 minutes) on blood pressure, peripheral hemodynamics, and urinary NO 3 − 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 NO 3 − excretion increased by 131.8±39.5% after l -arginine ( P <.05) but only by 32.3±17.2% after PGE 1 ( P =NS). Urinary cGMP excretion increased by 198.7±84.9% after l -arginine ( P <.05) and by 94.2±58.8% after PGE 1 ( P =NS). Both urinary index metabolites were unchanged by placebo. Conclusions We conclude that intravenous l -arginine induces NO-dependent peripheral vasodilation in patients with critical limb ischemia. These effects are paralleled by increased urinary NO 3 − and cGMP excretion, indicating an enhanced systemic NO production. Increased urinary NO 3 − excretion may be a sum effect of NO synthase substrate provision ( l -arginine) and increased shear stress (PGE 1 and l -arginine).