Beneficial effects of L -arginine supplementation in experimental hyperlipemia-hyperglycemia in the hamster

Abstract

The objective of this study was to evaluate whether administration of L-arginine, the substrate for nitric oxide synthesis, was able to ameliorate the endothelial dysfunction and the morphological changes induced by the combined insult of hyperlipemia and hyperglycemia. To this purpose, golden Syrian hamsters were rendered simultaneously hyperlipemic and diabetic (HD group) for 24 weeks, and then orally treated with 622.14 mg/kg per day L-arginine, for 12 weeks (HD + L-arg group). The following assays were carried out: (1) spectrophotometric: concentrations of circulating glucose, cholesterol, and creatinine, the activity of angiotensin-converting enzyme (ACE), and the osmotic fragility of erythrocyte plasmalemma; (2) myographic: the endothelium-dependent and -independent relaxation of the resistance arteries (i.d. 210-250 microm) to 10(-8) to 10(-4) M acetylcholine (ACh) or sodium nitroprusside (SNP); and (3) electron-microscopic: the ultrastructure of the resistance arteries, myocardium, and kidney glomeruli, which are main targets of hypertensive complications. The results showed that oral supplementation with L-arginine in simultaneous hyperlipemia-hyperglycemia induced in hamsters had favorable effects on: (1) homeostasis, i.e., diminished the concentration of circulating glucose (by ~63%) and cholesterol (by approximately 10%), reduced the ACE activity (by approximately 45%), and lowered the osmotic fragility of erythrocyte plasmalemma (as marker for the oxidative stress in plasma); (2) mesenteric resistance arteries, which showed (in 10(-4) M ACh) an improved endothelium-dependent relaxation (72.40+/-4.6% in the HD + L-arg group vs 61.90+/-1.45% in the HD group) and a reduced thickness (approximately 1.32-fold) of the smooth muscle cells' extracellular matrix; and (3) the heart, which displayed approximately 16% diminishing of the thickness of the left ventricular wall, and an apparently normal structure of the myocardium; the restoration of the thickness of the pericapillary extracellular matrix to almost normal dimensions was also observed. Administration of L-arginine did not modify the high level of plasma creatinine determined for the HD group (approximately 48% increased vs control group) and had no effect on the thickened, nodular basal lamina of the kidney capillaries. The results indicate that endothelial dysfunction established in combined hyperlipemia-diabetes is distinctive for each vascular bed (mesenteric arterioles, heart capillaries, kidney glomerular capillaries), and there is a reversible stage of the dysfunction in which L-arginine oral supplementation induced beneficial effects.

l‐Arginine ameliorates oxidative stress in alloxan‐induced experimental diabetes mellitus

“…Thus the ROS-scavenging property of l-arginine and polyamines (Lass et al, 2002), together with their ability to sustain and/or spare endogenous antioxidants, including SOD and CAT (Tables 2 and 3), and to increase NO and thiol groups (Faldetta et al, 2002), may help to explain the antioxidative effect of l-arginine. Thus, the present results indicate that treatment with l-arginine may counteract oxidative stress and ameliorate the metabolic disorder associated with diabetes mellitus by modulation of endogenous antioxidants (Mendez and Palomar-Morales, 1999;Popov et al, 2002).…”

“…In conclusion, the contribution of l-arginine to the protection and control of alloxan-induced oxidant stress in the liver and brain and its ability to modulate the glucose and cholesterol levels in experimental diabetes is most likely attributed to its direct, NO-dependent antioxidant capacity and NO-independent pathways such as the formation of polyamines (Popov et al, 2002). The molecular mechanism of NO, polyamines and their precursor l-arginine in stimulating insulin synthesis and release, activating insulin receptors (Hamer et al, 2002) and endogenous antioxidants, is critical in diabetes mellitus and requires further investigation.…”

Double transgenic mice with Type 1 diabetes mellitus develop somatic, metabolic and vascular disorders

“…The latter is a biomarker currently used to evaluate oxidative processes. In RBC of diabetic patients, increased osmotic fragility of RBC was reported [9] a feature also manifest in animal models of streptozotocin diabetes associated with hyperlipemia [10]. This effect is due to the high circulating glucose levels that caused RBC membrane lipid peroxidation and increased fragility.…”

Implications of Early Structural-Functional Changes in the Endothelium for Vascular Disease

“…85 L-arginine supplementation amends NO-induced EC dysfunction in human diabetes and in hyperlipemic-diabetic hamsters. 86,87 A direct approach foreseen in the treatment of CVD is the specific targeting of endothelial altered mechanisms and molecules, because the ECs are major actors involved in all stages of these diseases and have the advantage of being easily accessible for vascular-delivered drugs.…”