Endothelial dysfunction in hypercholesterolemia is corrected by L-arginine.
Hypercholesterolemia attenuates endothelium-dependent vasorelaxation and augments the responses to vasoconstrictor agents. Both effects are largely due to a reduction in the release of endothelium-derived relaxing factor. Since endothelium-derived relaxing factor is now known to be nitric oxide derived from the metabolism of L-arginine, we hypothesized that the abnormal vascular response in hypercholesterolemia could be corrected by supplying the precursor to EDRF, L-arginine. In a series of studies, we have found that conduit and resistance vessels of hypercholesterolemic animals demonstrate endothelial dysfunction which is reversed after exposure to high concentrations of exogenous L-arginine. The experiments suggest that hypercholesterolemia induces a reversible dysfunction of arginine availability or metabolism.
Cooke
J P
JP
Division of Cardiovascular Medicine, Falk Cardiovascular Research Center, Stanford University School of Medicine, California.
Dzau
J
J
Creager
A
A
D000818:Animals; D001011:Aorta / Q000502:physiology; D001120:Arginine / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D001488:Basilar Artery / Q000502:physiology; D004036:Diet, Atherogenic; D004730:Endothelium, Vascular / Q000502:physiology*; D005263:Femoral Artery / Q000502:physiology*; D006614:Hindlimb; D006937:Hypercholesterolemia / Q000503:physiopathology*; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D001120:Arginine