Bioassay discrimination between nitric oxide (NO.) and nitroxyl (NO-) using L-cysteine.
Nitroxyl (NO-) is the one-electron reduction product of nitric oxide (NO.). Recently, NO- generating compounds were shown to possess potent vasorelaxant activity and this was attributed to the ready conversion of NO- to NO.. Because of its metastable character, direct chemical detection of NO- or its conjugated acid, HNO, has not been accomplished yet. In order to gain further insight into the cellular mode of action of NO- generating compounds we aimed at finding a means to discriminate NO- from NO. by bioassay. Using isolated rat aortic rings in organ baths, we here show that high concentrations of L-cysteine cause complete inhibition of the vasorelaxant response to NO- (generated from Angeli's salt and sodium nitroxyl) whereas responses to authentic NO. and S-nitrosocysteine are largely enhanced. Preliminary results indicate that the inhibition by L-cysteine of NO- activity may be mediated in part by enzymatic and non-enzymatic mechanisms. Whether or not NO- generating compounds will have promising therapeutic potential as a new class of NO.- donors will not least depend on their interference with enzymatic routes susceptible to inhibition by NO-.
Pino
R Z
RZ
Department of Nitric Oxide Research, Schwarz Pharma AG, Monheim, FRG.
Feelisch
M
M
D000818:Animals; D001011:Aorta; D001681:Biological Assay; D003545:Cysteine / Q000737:chemistry; D005609:Free Radicals; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular; D009569:Nitric Oxide / Q000032:analysis*; D009589:Nitrogen Oxides / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar
D005609:Free Radicals; D009589:Nitrogen Oxides; D009569:Nitric Oxide; C039900:nitroxyl; D003545:Cysteine