Indices of activity of the nitric oxide system in hemodialysis patients

Arginine deficiency and/or increased levels of circulating nitric oxide (NO ) synthesis (NOS) inhibitors can cause reduced NOS, which may contribute to hypertension in patients with end-stage renal disease (ESRD). To test thes e hypotheses, NO oxidation products (NO2 + NO3 = NOx) and cyclic guanosine monophosphate (cGMP), the vasodilatory second messenger of NO, were measure d in the blood, urine, and dialysate effluent of hemodialysis (HD) patients and compared with the blood and urine of healthy subjects. The subjects at e a controlled low-nitrate diet (similar to 330 mu mol/d) for 48 hours befo re and during blood, dialysis effluent, and 24-hour urine collection. NO, o utput was significantly reduced in HD patients versus controls (552 +/- 51 v824 +/- 96 mu mol/24 h; P < 0.001), whereas cGMP output was not low versus controls. Plasma arginine level was normal and plasma levels of citrulline and the endogenous NOS inhibitor, asymmetric dimethylarginine (ADMA), were markedly elevated in patients with ESRD versus controls. Systolic blood pr essure was greater in HD patients compared with controls despite concurrent antihypertensive therapy in most patients with ESRD. These studies suggest NO production is low in patients with ESRD undergoing HD, possibly because of the increased ratio of plasma ADMA to arginine. (C) 1999 by the Nationa l Kidney Foundation, Inc.