dimethylarginine and Bone-Diseases--Metabolic

The Cardiorenal Syndrome type 4 (CRS-4) defines a pathological condition in which a primary chronic kidney disease (CKD) leads to a chronic impairment of cardiac function. The pathophysiology of CRS-4 and the role of arterial stiffness remain only in part understood. Several uremic toxins, such as uric acid, phosphates, advanced glycation end-products, asymmetric dimethylarginine, and endothelin-1, are also vascular toxins. Their effect on the arterial wall may be direct or mediated by chronic inflammation and oxidative stress. Uremic toxins lead to endothelial dysfunction, intima-media thickening and arterial stiffening. In patients with CRS-4, the increased aortic stiffness results in an increase of cardiac workload and left ventricular hypertrophy whereas the loss of elasticity results in decreased coronary artery perfusion pressure during diastole and increased risk of myocardial infarction. Since the reduction of arterial stiffness is associated with an increased survival in patients with CKD, the understanding of the mechanisms that lead to arterial stiffening in patients with CRS4 may be useful to select potential approaches to improve their outcome. In this review we aim at discussing current understanding of the pathways that link uremic toxins, arterial stiffening and impaired cardiac function in patients with CRS-4.

Topics: Aorta; Arginine; Autonomic Nervous System Diseases; Bone Diseases, Metabolic; Cardio-Renal Syndrome; Cardiovascular Diseases; Chronic Disease; Endothelium, Vascular; Glycation End Products, Advanced; Humans; Inflammation; Myocardial Infarction; Oxidative Stress; Phosphorus; Renal Insufficiency, Chronic; Toxins, Biological; Tunica Intima; Uric Acid; Vascular Stiffness; Vasculitis

Previous studies have indicated that the plasma concentration of nitric oxide synthase inhibitor, asymmetric dimethylarginine (ADMA), was increased in postmenopausal women. In the study reported here, we tested the relationship between the decrease of bone mineral density (BMD) and ADMA concentration in ovariectomized (OVX) rats. Ovariectomized rats at 8 months of age were treated with 17beta-estradiol (10 or 30 microg/kg of body weight/day, s.c.) or L-arginine (300 mg/kg/day, i.p.) for 12 weeks (n = 10 for each group). Pre- and posttreatment total BMD, posttreatment plasma nitrite/nitrate and ADMA concentrations, and posttreatment BMD in the lumbar part of the spine (L4-L6), femurs, and tibias were examined. Ovariectomy caused a significant decrease in several BMD indexes, which was reversed by estrogen treatment (P < 0.05). Plasma nitrite/nitrate concentration was significantly decreased in OVX rats, but was restored by estrogen treatment (P < 0.05). There were no differences in the plasma concentration of ADMA in OVX or estrogen-treated rats. L-Arginine had no effect on plasma nitrite/nitrate concentration and BMD in OVX rats. These results suggest that ovariectomy does not influence the plasma concentration of ADMA, and that ADMA is not involved in ovariectomy-induced osteopenia in rats.

Topics: Animals; Arginine; Bone and Bones; Bone Density; Bone Diseases, Metabolic; Estrogens; Female; Nitrates; Nitrites; Ovariectomy; Rats; Rats, Sprague-Dawley