We describe in-vitro and in-vivo evidence that NO synthesis can be inhibited by an endogenous compound, N(G),N(G)-dimethylarginine (asymmetrical dimethylarginine, ADMA). In man, this inhibitor is found in plasma and more than 1 0 mg is excreted in urine over 24 h. However, in patients with end-stage chronic renal failure, who have little or no urine output, elimination is blocked and circulating concentrations of the inhibitor rise sufficiently to inhibit NO synthesis.

Accumulation of endogenous ADMA, leading to impaired NO synthesis, might contribute to the hypertension and immune dysfunction associated with chronic renal failure.