L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans.
Endothelium-dependent vasodilation is impaired in hypercholesterolemia, even before the development of atherosclerosis. The purpose of this study was to determine whether infusion of L-arginine, the precursor of the endothelium-derived relaxing factor, nitric oxide, improves endothelium-dependent vasodilation in hypercholesterolemic humans. Vascular reactivity was measured in the forearm resistance vessels of 11 normal subjects (serum LDL cholesterol = 2.76 +/- 0.10 mmol/liter) and 14 age-matched patients with hypercholesterolemia (serum LDL cholesterol = 4.65 +/- 0.36 mmol/liter, P < 0.05). The vasodilative response to the endothelium-dependent vasodilator, methacholine chloride, was depressed in the hypercholesterolemic group, whereas endothelium-independent vasodilation, induced by nitroprusside, was similar in each group. Intravenous administration of L-arginine augmented the forearm blood flow response to methacholine in the hypercholesterolemic individuals, but not in the normal subjects. L-arginine did not alter the effect of nitroprusside in either group. D-arginine had no effect on forearm vascular reactivity in either group. It is concluded that endothelium-dependent vasodilation is impaired in hypercholesterolemic humans. This abnormality can be improved acutely by administration of L-arginine, possibly by increasing the synthesis of endothelium-derived relaxing factor.
Creager
M A
MA
Vascular Medicine and Atherosclerosis Unit, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Gallagher
S J
SJ
Girerd
X J
XJ
Coleman
S M
SM
Dzau
V J
VJ
Cooke
J P
JP
D000328:Adult; D001120:Arginine / Q000097:blood / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006937:Hypercholesterolemia / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D007328:Insulin; D016210:Methacholine Chloride; D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine