EFFECTS OF DIETARY L-ARGININE ON ATHEROSCLEROSIS AND ENDOTHELIUM-DEPENDENT VASODILATATION IN THE HYPERCHOLESTEROLEMIC RABBIT - RESPONSE ACCORDING TO TREATMENT DURATION, ANATOMIC SITE, AND SEX

Background Nitric oxide (NO) may protect arteries against atherosclero sis. In the present study, we examined whether dietary L-arginine, the precursor of NO, could chronically preserve endothelium-dependent vas odilation in vivo and/or limit atherogenesis. Methods and Results Rabb its were randomized according to sex to receive 2% dietary cholesterol , with or without L-arginine (2.25% solution), for 7 or 14 weeks. Hind limb vasodilator responses to acetylcholine and nitroprusside were mea sured with an electromagnetic flow probe. Atherosclerosis was measured with planimetry of aortic lesions stained with Oil-Red-O. In rabbits administered L-arginine, plasma arginine levels increased to 483+/-30 mu mol/L at 3 weeks (mean+/-SEM, P<.0001 versus control animals) but d eclined to 224+/-25 mu mol/L at 14 weeks (NS versus control animals). At 7 weeks, peak hindlimb conductance in response to acetylcholine in cholesterol-fed males was 249+/-49% of baseline compared with 332+/-9% in control animals (P=.04), but peak response in arginine-fed rabbits (314+/-24%) did not differ from that of control animals. At 14 weeks, peak responses to acetylcholine were equally reduced in males fed cho lesterol with (266+/-21%, P=.02 versus control) or without (263+/-13%, P=.01 versus control) L-arginine. Similar impairment of endothelium-d ependent vasodilatation was seen in females at 14 weeks. Vasodilator r esponses to nitroprusside did not differ from those of control animals in any treatment group. After 14 weeks, atherosclerosis was less in t he descending aorta of arginine-fed males (16+/-4% surface area) than that of males fed cholesterol only (42+/-8%, or in females. Conclusion s Dietary L-arginine supplementation causes an early rise in plasma ar ginine levels, with limitation of atherosclerosis in the descending ao rta and preservation of endothelium-dependent vasodilatation in resist ance arteries, but this treatment effect is not sustained. Dietary L-a rginine may not be of long-term benefit in the prevention of atheroscl erosis in humans.