In normotensive patients with heart failure plasma ADMA concentrations are markedly increased and related to reduced renal perfusion. Thus accumulation of this endogenous nitric oxide inhibitor may play a role in renal pathology in these patients.

Abstract. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase. Its concentration is elevated in patients with end-stage renal disease (ESRD), in part because it is excreted via the kidneys. In this study, the plasma concentrations of ADMA, symmetric dimethylarginine, and L-arginine were determined in relation to plasma nitrate levels (as an index of NO formation) for a group of 80 patients with ESRD. The effects of two treatment methods, i.e., hemodialysis (HD) and peritoneal dialysis (PD), and the role of the presence of atherosclerotic disease were evaluated. Forty-three patients receiving HD and 37 patients receiving PD were compared with healthy control subjects. Plasma L-arginine and dimethylarginine levels were determined by HPLC, using precolumn derivatization with o-phthaldialdehyde. Plasma nitrate levels were determined by gas chromatography-mass spectrometry. Predialysis ADMA concentrations in HD-treated patients were approximately sixfold higher than those in the control group (6.0 ± 0.5 versus 1.0 ± 0.1 μmol/L; P < 0.05). Plasma nitrate concentrations were significantly lower in HD-treated patients, which suggests that ADMA may inhibit NO synthase. In contrast, plasma ADMA levels and nitrate concentrations in PD-treated patients were similar to those in control subjects. Plasma L-arginine concentrations were not significantly decreased in patients with ESRD. ADMA concentrations were significantly decreased 5 h after HD, compared with baseline values. ADMA levels were significantly higher in HD-treated patients with manifest atherosclerotic disease than in HD-treated patients without atherosclerotic disease (7.31 ± 0.70 versus 3.95 ± 0.52 μmol/L; P < 0.05). This study confirms that ADMA is accumulated in ESRD. PD-treated patients exhibit significantly lower ADMA levels than do HD-treated patients. Accumulation of ADMA may be a risk factor for the development of endothelial dysfunction and cardiovascular disease in patients with ESRD.

Objectives-In rats with adjuvant arthritis measurements were taken of the urinary excretion ofnitrate, reflecting endogenous nitric oxide (NO) formation, and cyclic guanosine monophosphate (cGMP Materials and methods ANIMALS AND ARTHRITIS INDUCTIONTwelve male Sprague Dawley rats with adjuvant arthritis and 12 non-arthritic rats of the same strain and age were purchased from Charles River, Cleon, France. Adjuvant arthritis was induced as described by Gouret et al.' 0 As a control group 12 non-arthritic rats of the same strain were held under the same conditions. Both groups received unlimited amounts of tap water (nitrate concentration <1 -6 ,umol/ 1, nitrite concentration <0-1 ,umol/l) and food Eggersmann, Rinteln, Germany). EXPERIMENTAL PROTOCOLAt day 20 after arthritis induction secondary arthritic lesions at all four paws, penis and tip of the nose of each rat were examined according to the following score (maximal value/animal = 16): 0 = No erythema and no inflammation; 1 = Distinct to moderate erythema of 1 paw or swelling of 1 joint at one paw; 2 = Swelling of 2-3 joints at one paw or swelling ofpenis or tip of the nose; 3 = Swelling of 4-5 joints at one paw or extensive erythema and swelling of one paw.Twenty four hour urine samples were collected in metabolism cages at day 20 after inoculation; at the same day the body weight of each rat was assessed. Bacterial growth in the urine was prevented by addition of 2 ml 2-propanol into the collection tube. ANALYSESUrinary nitrate was determined by a gas chromatographic method, based on a reaction