Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure.
Nitric oxide (NO), synthesised from L-arginine, contributes to the regulation of blood pressure and to host defence. We describe in-vitro and in-vivo evidence that NO synthesis can be inhibited by an endogenous compound, NG,NG-dimethylarginine (asymmetrical dimethylarginine, ADMA). In man, this inhibitor is found in plasma and more than 10 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.
Vallance
P
P
Wellcome Research Laboratories, Beckenham, Kent, UK.
Leone
A
A
Calver
A
A
Collier
J
J
Moncada
S
S
D000328:Adult; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001120:Arginine / Q000031:analogs & derivatives* / Q000032:analysis / Q000494:pharmacology / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D005542:Forearm / Q000098:blood supply; D006168:Guinea Pigs; D006801:Humans; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine