L-arginine restores cholesterol-attenuated microvascular responses in the rat cremaster.
The role of L-arginine in the reversal of cholesterol-induced endothelial dysfunction was studied in the cremaster muscle microcirculation. In vivo television microscopy was used to measure microvascular diameters and macromolecular leakage. Male Sprague-Dawley rats were fed either 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 cholesterol diet caused a decreased third-order arteriole dilator response to both acetylcholine and serotonin. This decreased responsiveness occurred in the presence of a higher plasma concentration of L-arginine and an increased ratio of L-arginine to its metabolite L-citrulline. The attenuation to both agonists was reversed by intravenous infusion of the nitric oxide precursor L-arginine (30-mg/kg bolus and 10-mg/kg/min continuous infusion). The cholesterol diet also decreased the postcapillary macromolecular leakage response to serotonin, and again this effect was reversed by L-arginine infusion. D-Arginine infusion had no restorative effect with either agonist in the cholesterol animals. Further experimentation with the nitric oxide production inhibitor N omega-nitro-L-arginine methyl ester demonstrated an inhibition of aretriolar dilation to acetylcholine, but there was no inhibition of dilation or macromolecular leakage to serotonin. Thus, it is probable that serotonin-induced leakage as well as dilation was not caused by stimulation of nitric oxide. These results suggest that L-arginine restores both nitric oxide-dependent and -independent dilation as well as macromolecular leakage in cholesterol-fed rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Center for Applied Microcirculatory Research, University of Louisville, Ky. 40292.
D A
DA
Schuschke
F N
FN
Miller
D G
DG
Lominadze
R C
RC
Feldhoff
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000503:physiopathology*; D008297:Male; D018715:Microscopy, Video; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D013690:Television
D002791:Cholesterol, Dietary; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine