L-arginine induces nitric oxide-dependent vasodilation in patients with critical limb ischemia : a randomized, controlled study

• Published in: Circulation (New York, N.Y.) Vol. 93; no. 1; pp. 85 - 90
• Main Authors: BODE-BÖGER, S. M, BÖGER, R. H, ALFKE, H, HEINZEL, D, TSIKAS, D, CREUTZIG, A, ALEXANDER, K, FRÖLICH, J. C
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 1996; American Heart Association, Inc
• Subjects: Aged; Arginine - therapeutic use; Arterial Occlusive Diseases - complications; Arterial Occlusive Diseases - drug therapy; Arterial Occlusive Diseases - physiopathology; Biological and medical sciences; Cardiovascular system; Extremities - blood supply; Humans; Injections, Intravenous; Ischemia - drug therapy; Ischemia - etiology; Ischemia - physiopathology; Male; Medical sciences; Middle Aged; Nitric Oxide - metabolism; Pharmacology. Drug treatments; Vasodilation - drug effects; Vasodilator agents. Cerebral vasodilators; Human; Vasodilator agent; Intravenous administration; Treatment efficiency; Lower limb; Vasodilation; Chemotherapy; Treatment; Arginine; Ischemia; Double blind study; Occlusive arterial disease; Arterial disease of the limb; Mechanism of action; Nitrogen Oxides
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.93.1.85

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 E1 (PGE1) induces peripheral vasodilation via stimulating prostacyclin receptors. We investigated the effects of one intravenous infusion of L-arginine (30 g, 60 minutes) or PGE1 (40 microgram, 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 PGE1 (+31.0 +/- 10.2%, P<.05) but not by placebo (+4.3 +/- 13.0%, P=NS). Urinary NO3- excretion increased by 131.8 +/- 39.5% after L-arginine (P<.05) but only by 32.3 +/- 17.2% after PGE1 (P=NS). Urinary cGMP excretion increased by 198.7 +/- 84.9% after L-arginine (P<.05) and by 94.2 +/- 58.8% after PGE1 (P=NS). Both urinary index metabolites were unchanged by placebo. We conclude that intravenous L-arginine induces 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. Increased urinary NO3- excretion may be a sum effect of NO synthase substrate provision (L-arginine) and increased shear stress (PGE1 and L-arginine).