Abstract
Acute administration of the amino acid L-arginine has been shown to reverse cholesterol attenuated endothelium-dependent vasodilation. A role for chronic L-arginine as a protectant against cholesterol-induced endothelial dysfunction was studied in the rat cremaster muscle microcirculation. Pellets containing L-arginine (200 mg, 3 week release) and corresponding placebo were implanted subcutaneously in male Sprague-Dawley rats. The rats were then fed either a normal chow diet or chow diet supplemented with 1% cholesterol and 0.5% cholic acid for 3 weeks prior to in vivo experimentation. In vivo television microscopy was used to quantitate microvascular diameter changes. The third order dilator response to both acetylcholine and serotonin was significantly greater in the L-arginine treated group fed the high cholesterol diet compared to the placebo treated group on the same diet. There was no difference in dilator response between the L-arginine treated cholesterol rats and either L-arginine or placebo treated normal diet rats. The cholesterol fed group had higher serum cholesterol and low density lipoprotein (LDL) levels than the normal diet group but there was no difference in lipoprotein profiles between the placebo and L-arginine treated rats for either the cholesterol or normal diet groups. L-arginine did not prevent fat deposition in the liver or the increase in the liver wt./body wt. ratio associated with high dietary cholesterol. The results demonstrate that chronic L-arginine has a protective role against cholesterol-attenuated microvascular vasodilator function but that this protection does not extend to the alteration of serum levels of lipoproteins or the development of fatty livers associated with the hypercholesterolemic diet.