L-ARGININE RESTORES CHOLESTEROL-ATTENUATED MICROVASCULAR RESPONSES INTHE RAT CREMASTER

The role of L-arginine in the reversal of cholesterol-induced endothel ial dysfunction was studied in the cremaster muscle microcirculation. In vivo television microscopy ws used to measure microvascular diamete rs and macromolecular leakage. Male Sprague-Dawley rats were fed eithe r a normal chow diet or a diet supplemented with 1% cholesterol and 0. 5% cholic acid for 3 weeks prior to in vivo experimentation. The chole sterol diet caused a decreased third-order arteriole dilator response to both acetylcholine and serotonin. This decreased responsiveness occ urred in the presence of a higher plasma concentration of L-arginine a nd an increased ratio of L-arginine to its metabolite L-citrulline. Th e attenuation to both agonists was reversed by intravenous infusion of the nitric oxide precursor L-arginine (30-mg/kg bolus and 10-mg/kg/mi n continuous infusion). The cholesterol diet also decreased the postca pillary macromolecular leakage response to serotonin, and again this e ffect was reversed by L-arginine infusion. D-Arginine infusion had no restorative effect with either agonist in the cholesterol animals. Fur ther experimentation with the nitric oxide production inhibitor N-omeg a-nitro-L-arginine methyl ester demonstrated an inhibition of aretriol ar dilation to acetylcholine, but there was no inhibition of dilation or macromolecular leakage to serotonin. Thus, it is probable that sero tonin-induced leakage as well as dilation was not caused by stimulatio n of nitric oxide. These results suggest that L-arginine restores both nitric oxide-dependent and -independent dilation as well as macromole cular leakage in cholesterol-fed rats. L-Arginine probably acts both a s a precursor to nitric oxide and in another as yet undefined capacity which is important for nitric oxide-independent dilation and macromol ecular leakage.