Arginine restores cholinergic relaxation of hypercholesterolemic rabbit thoracic aorta.
BACKGROUND
Reduced synthesis of endothelium-derived relaxing factor (EDRF) may explain impaired endothelium-dependent vasodilation in hypercholesterolemia. Accordingly, we designed studies to determine if endothelium-dependent relaxation in hypercholesterolemic rabbits may be restored by supplying L-arginine, the precursor of EDRF.


RESULTS
Normal or hypercholesterolemic rabbits received intravenous L-arginine (10 mg/kg/min) or vehicle for 70 minutes. Subsequently, animals were killed, thoracic aortas were harvested, and vascular rings were studied in vitro. Rings were contracted by norepinephrine and relaxed by acetylcholine chloride or sodium nitroprusside. Vasorelaxation was quantified by determining the maximal response (expressed as percent relaxation of the contraction) and the ED50 (dose of drug inducing 50% relaxation; expressed as -log M). In vessels from hypercholesterolemic animals receiving vehicle, there was a fivefold rightward shift in sensitivity to acetylcholine compared with normal animals (p = 0.05, n = 5 in each group). In vessels from hypercholesterolemic animals, L-arginine augmented the maximal response to acetylcholine (83 +/- 16% versus 60 +/- 15%, p = 0.04 versus vehicle) and increased the sensitivity to acetylcholine (ED50 value: 6.7 +/- 0.2 versus 6.2 +/- 0.2, p less than 0.05 versus vehicle). Arginine did not affect maximal and EC50 responses to acetylcholine in vessels from normal animals. Arginine did not potentiate endothelium-independent responses in either group.


CONCLUSIONS
We conclude that the endothelium-dependent relaxation is normalized in hypercholesterolemic rabbit thoracic aorta by in vivo exposure to L-arginine, the precursor for EDRF.
Cooke
J P
JP
Division of Vascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston.
Andon
N A
NA
Girerd
X J
XJ
Hirsch
A T
AT
Creager
M A
MA
D000818:Animals; D001013:Aorta, Thoracic; D001120:Arginine / Q000378:metabolism / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006937:Hypercholesterolemia / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D011817:Rabbits; D014664:Vasodilation / Q000502:physiology
D009569:Nitric Oxide; D001120:Arginine