S-nitroso-albumin carries a thiol-labile pool of nitric oxide, which causes venodilation in the rat.
It is now established that S-nitroso-albumin (SNO-albumin) circulates at low nanomolar concentrations under physiological conditions, but concentrations may increase to micromolar levels during disease states (e.g., cirrhosis or endotoxemia). This study tested the hypothesis that high concentrations of SNO-albumin observed in some diseases modulate vascular function and that it acts as a stable reservoir of nitric oxide (NO), releasing this molecule when the concentrations of low-molecular-weight thiols are increased. SNO-albumin was infused into rats to increase the plasma concentration from <50 nmol/l to approximately 4 micromol/l. This caused a 29 +/- 6% drop in blood pressure, 20 +/- 4% decrease in aortic blood flow, and a 25 +/- 14% reduction of renal blood flow within 10 min. These observations were in striking contrast to those of an infused arterial vasodilator (hydralazine), which increased aortic blood flow, and suggested that SNO-albumin acts primarily as a venodilator in vivo. This was confirmed by the observations that glyceryl trinitrate (a venodilator) led to similar hemodynamic changes and that the hemodynamic effects of SNO-albumin are reversed by infusion of colloid. Infusion of N-acetylcysteine into animals with artificially elevated plasma SNO-albumin concentrations led to the rapid decomposition of SNO-albumin in vivo and reproduced the hemodynamic effects of SNO-albumin infusion. These data demonstrate that SNO-albumin acts primarily as a venodilator in vivo and represents a stable reservoir of NO that can release NO when the concentrations of low-molecular-weight thiols are elevated.
Orie
Nelson N
NN
Centre for Hepatology, Dept. of Medicine, Royal Free and Univ. College Medical School, Univ. College London, London NW3 2PF, UK.
Vallance
Patrick
P
Jones
Dean P
DP
Moore
Kevin P
KP
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004355:Drug Stability; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008970:Molecular Weight; D009569:Nitric Oxide / Q000378:metabolism*; D009603:Nitroso Compounds / Q000494:pharmacology*; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014680:Veins / Q000502:physiology*
D009603:Nitroso Compounds; C091665:S-nitrosoalbumin; D013438:Sulfhydryl Compounds; D014665:Vasodilator Agents; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; D000111:Acetylcysteine