Oral L-arginine improves endothelium-dependent dilatation and reduces monocyte adhesion to endothelial cells in young men with coronary artery disease.
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.
Adams
M R
MR
Department of Cardiolgoy, Royal Prince Alfred Hospital, Sydney, Australia.
McCredie
R
R
Jessup
W
W
Robinson
J
J
Sullivan
D
D
Celermajer
D S
DS
D000284:Administration, Oral; D000328:Adult; D001120:Arginine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001798:Blood Proteins / Q000737:chemistry; D001916:Brachial Artery / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis; D011446:Prospective Studies; D014471:Umbilical Veins; D014664:Vasodilation / Q000187:drug effects*
D001798:Blood Proteins; D008055:Lipids; D009569:Nitric Oxide; D001120:Arginine