IN-VIVO TRANSFER OF NITRIC-OXIDE BETWEEN A PLASMA PROTEIN-BOUND RESERVOIR AND LOW-MOLECULAR-WEIGHT THIOLS

Plasma albumin reacts with nitric oxide (NO) to form the bioactive add uct, S-nitroso-albumin (S-NO-albumin). The limited intracellular acces s of S-NO-albumin suggests the need for a vascular transfer mechanism of NO from a large plasma S-NO-albumin pool to effect biologic functio n. To study the role of low molecular weight (LMW) thiols in NO transf er in vivo, we administered intravenous S-NO-albumin (1-300 mnol/kg) t o rabbits before and after an intravenous infusion of L-cysteine or N- acetyl-L-cysteine. S-NO-albumin produced dose-dependent hypotension th at was significantly augmented by prior infusion of either LMW thiol. LMW thiol infusion significantly accelerated the rate of onset and red uced the duration of action of the hypotension induced by S-NO-albumin . The hemodynamic effects of S-NO-albumin after pretreatment with LMW thiols were mimicked by administration of the corresponding LMW S-nitr osothiol. The transfer of NO from albumin to L-cysteine was directly m easured in rabbit plasma using a novel technique that couples high per formance liquid chromatography to electrochemical detection. These dat a demonstrate that NO exchange between plasma protein thiolbound NO an d available LMW thiol pools (transnitrosation) occurs in vivo.