title: S,S'-dinitrosobucillamine, a new nitric oxide donor, induces a better vasorelaxation than other S-nitrosothiols.
abstract: S-nitrosothiols (RSNO) are considered as potential drugs for delivering nitric oxide (NO) or related species in cardiovascular disorders associated with decrease in NO bioavailability. We have synthesized a new RSNO, i.e. S,S'-dinitrosobucillamine (BUC(NO)2), which combines in its structure two S-mononitrosothiols, S-nitroso-N-acetylpenicillamine (SNAP) and S-nitroso-N-acetylcysteine (NACNO). Synthesized BUC(NO)2 was structurally characterized using high-performance liquid chromatography/mass spectrometry (HPLC/MS), (1)H nuclear magnetic resonance ((1)H NMR), infrared (IR) and UV-visible spectroscopies, and thermal analysis; resulting data are consistent with the expected structure. The vasorelaxant effect of BUC(NO)2 was evaluated using isolated rat aortic rings and compared to SNAP, NACNO, and to an equimolar mixture of NACNO plus SNAP in order to mimic the number of NO contained in a BUC(NO)2 molecule. BUC(NO)2 (pD2=7.8±0.1) was more potent in vasorelaxation than NACNO (pD2=6.4±0.2), SNAP (pD2=6.7±0.1) and the mixture of SNAP plus NACNO (pD2=6.7±0.2). The release of NO from BUC(NO)2 was 6-fold that of the basal value and significantly higher than the release of NO from the SNAP plus NACNO mixture (4-fold increase versus basal value). Finally, the role of protein disulfide isomerase (PDI) in BUC(NO)2 metabolism was investigated. Vasorelaxant effect (pD2=6.8±0.2) and NO release decreased in the presence of a PDI inhibitor (both P<0.05 versus BUC(NO)2). In conclusion, BUC(NO)2 releases a larger amount of NO into the aorta, partially through PDI activation, and induces vasorelaxation at lower concentrations than other RSNO previously reported.
authors.affiliation: Université de Lorraine, CITHÉFOR - EA 3452, Faculté de Pharmacie, BP 80403, 54001 Nancy Cedex, France.
authors.forename: Fatima
authors.initials: F
authors.lastname: Dahboul
authors.affiliation: Université de Lorraine, CITHÉFOR - EA 3452, Faculté de Pharmacie, BP 80403, 54001 Nancy Cedex, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Perrin-Sarrado
authors.affiliation: Université de Lorraine, CITHÉFOR - EA 3452, Faculté de Pharmacie, BP 80403, 54001 Nancy Cedex, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Boudier
authors.affiliation: Université de Lorraine, CITHÉFOR - EA 3452, Faculté de Pharmacie, BP 80403, 54001 Nancy Cedex, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lartaud
authors.affiliation: Université de Lorraine et CNRS, Laboratoire Réactions et Génie des Procédés, UMR 7274, BP 20451, 54001 Nancy Cedex, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Schneider
authors.affiliation: Université de Lorraine, CITHÉFOR - EA 3452, Faculté de Pharmacie, BP 80403, 54001 Nancy Cedex, France. Electronic address: pierre.leroy@univ-lorraine.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Leroy
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D055598:Chemical Phenomena; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004355:Drug Stability; D066298:In Vitro Techniques; D008297:Male; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019704:Protein Disulfide-Isomerases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D026403:S-Nitrosothiols / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; C000593383:S,S'-dinitrosobucillamine; D026403:S-Nitrosothiols; D014665:Vasodilator Agents; D019704:Protein Disulfide-Isomerases; D003545:Cysteine; C026535:bucillamine
keywords: Physicochemical characterization; Protein disulfide isomerase; Rat aorta ring; S,S′-dinitrosobucillamine; Vasorelaxation