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 atherosclerosis. In the present study, we examined whether dietary L-arginine, the precursor of NO, could chronically preserve endothelium-dependent vasodilation in vivo and/or limit atherogenesis. Methods and Results Rabbits were randomized according to sex to receive 2% dietary cholesterol, with or without L-arginine (2.25% solution), for 7 or 14 weeks. Hindlimb vasodilator responses to acetylcholine and nitroprusside were measured 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 declined 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 cholesterol with (266+/-21%, P=.02 versus control) or without (263+/-13%, P=.01 versus control) L-arginine. Similar impairment of endothelium-dependent vasodilatation was seen in females at 14 weeks. Vasodilator responses to nitroprusside did not differ from those of control animals in any treatment group. After 14 weeks, atherosclerosis was less in the descending aorta of arginine-fed males (16+/-4% surface area) than that of males fed cholesterol only (42+/-8%, or in females. Conclusions Dietary L-arginine supplementation causes an early rise in plasma arginine levels, with limitation of atherosclerosis in the descending aorta and preservation of endothelium-dependent vasodilatation in resistance arteries, but this treatment effect is not sustained. Dietary L-arginine may not be of long-term benefit in the prevention of atherosclerosis in humans.