L-Arginine is the physiological substrate for nitric oxide synthesis by the vascular
endothelium. In hypercholesterolaemic rabbits, oral L-arginine reduces atheroma, improves
endothelium-dependent dilatation and reduces monocyte/endothelial cell adhesion. The
effect of oral L-arginine on endothelial physiology is unknown, however, in humans
with established atherosclerosis. In a prospective, double-blind, randomised crossover
trial, ten men aged 41 +/- 2 years with angiographically proven coronary atherosclerosis
took L-arginine (7 g three times per day) or placebo for 3 days each, with a washout
period of 10 days. After L-arginine, compared to placebo, plasma levels of arginine
were increased (318 +/- 18 vs. 124 +/- 9 mumol/l, P < 0.01) and endothelium-dependent
dilatation of the brachial artery (measured as the change in diameter in response
to reactive hyperaemia, using external vascular ultrasound) was improved (4.7 +/-
1.1 vs. 1.8 +/- 0.7%, P < 0.04). No changes were seen in endothelium-independent dilatation
of the brachial artery (measured as the change in diameter in response to sublingual
nitroglycerine), blood pressure, heart rate or fasting lipid levels. Serum from six
of the ten subjects after L-arginine and placebo was then added to confluent monolayers
of human umbilical vein endothelial cells for 24 h, before human monocytes obtained
by countercurrent centrifiguation elutriation were added and cell adhesion assessed
by light microscopy. Adhesion was reduced following L-arginine compared to placebo
(42 +/- 2 vs. 50 +/- 1%, P < 0.01). In young men with coronary artery disease, oral
L-arginine improves endothelium-dependent dilatation and reduces monocyte/endothelial
cell adhesion.