Dietary L-Arginine Normalizes Endothelin-Induced Vascular Contractions in Cholesterol-Fed Rabbits

Abstract

The endothelium regulates vascular function by releasing the vasodilator autacoid nitric oxide (NO) and the vasoconstrictor peptide endothelin-1 (ET-1). Impaired activity of NO as well as excessive activity of ET-1 have been demonstrated in hypercholesterolemia and atherosclerosis. Because dietary L-arginine can restore NO function and improve abnormal endothelium-dependent relaxation in hypercholesterolemic rabbits, we examined the effects of dietary supplementation with L-arginine in cholesterol-fed rabbits on endothelium-dependent vascular relaxation and ET-1-induced vascular contraction, as well as the systemic synthesis of ET-1. Rabbits were initially fed a diet enriched with 1% cholesterol for 4 weeks, followed by 0.5% cholesterol alone or supplemented with 2% L-arginine in drinking water during the next 12 weeks. Cholesterol feeding impaired endothelium-dependent relaxation of rabbit aortic rings ex vivo and increased urinary immunoreactive ET-1 excretion, along with decreased urinary nitrate excretion, an index of NO production. L-Arginine partially restored endothelium-dependent relaxation in parallel to increased urinary nitrate excretion and decreased urinary immunoreactive ET-1 excretion. Selective inhibition of ET-A receptors with BQ123 partially restored endothelium-dependent relaxation in hypercholesterolemic rabbits but had no effect on arterial rings from rabbits supplemented with L-arginine or from control animals. The contractile vascular response of aortic rings to exogenous ET-1 was increased in rabbits fed a high-cholesterol diet; this enhanced contractility to ET-1 was completely reversed by L-arginine. These data suggest that L-arginine restores endothelial function and normalizes the synthesis and vasoconstrictor response to ET-1 in hypercholesterolemia.

Reduced contribution of endothelin to the regulation of systemic and pulmonary vascular tone in severe familial hypercholesterolaemia

“…; Phivthong‐ngam et al . ; Cardillo et al . ) and disease‐related increases in ET action are sufficient to limit exercise hyperaemia (McEniery et al .…”

Effects of Cholesterol Diets on Vascular Function and Atherogenesis in Rabbits

“…Previous data showed that a 3‐week 0.3% cholesterol diet followed by either 0.3% or 0.5% cholesterol feeding for another 10 weeks induced 19.8%± 5.6% and 32.4%± 5.5% of aortic lipid lesions in the rabbits, respectively (19). Rabbits fed a 4‐week 1% cholesterol diet followed by a 12‐week 0.5% cholesterol diet showed impaired endothelium‐dependent relaxation in aortic rings ex vivo (24). Significantly impaired endothelium‐dependent vasodilation in the carotid artery was also found in rabbits with 8–10 weeks of 1% cholesterol feeding (25).…”

Lipids and endothelium‐dependent vasodilation—A review

“…Treatment with L-arginine has been shown to improve EDV without any alterations in serum cholesterol levels (202,(208)(209)(210)(211)(212)(213)(214). Also, different antioxidants or free-radical scavengers, such as probucol, superoxide dismutase, vitamin E, tomato carotenoids, and β-carotene, have positive effects on EDV in hypercholesterolemic animals (202,(215)(216)(217)(218)(219)(220)(221)(222)(223)(224)(225)(226)(227)(228).…”

“…Also, different antioxidants or free-radical scavengers, such as probucol, superoxide dismutase, vitamin E, tomato carotenoids, and β-carotene, have positive effects on EDV in hypercholesterolemic animals (202,(215)(216)(217)(218)(219)(220)(221)(222)(223)(224)(225)(226)(227)(228). Commonly used antihypertensive therapies, such as angiotensin-converting enzyme inhibition, calcium and α-receptor blockade, endothelin receptor blockade, and neuroendopetidase inhibition, all have positive effects on EVD (194,211,(229)(230)(231)(232)(233)(234)(235)(236)(237); a number of other drugs, such as heparin and estrogens (see Table 3) (238)(239)(240)(241)(242)(243)(244)(245) have also exhibited this effect.…”