S,S鈥?dinitrosobucillamine, a new nitric oxide donor, induces a better vasorelaxation than other S-nitrosothiols

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• 作者：Fatima Dahboul^a ; Caroline Perrin-Sarrado¹ ; ^a ; Ariane Boudier^a ; ¹ ; Isabelle Lartaud^a ; Raphaë ; l Schneider^b ; Pierre Leroy^a ; ^{pierre.leroy@univ-lorraine.fr" class="auth_mail}
• 关键词：AlbSNO ; S-nitrosoalbumin ; BUC(SH)2 ; bucillamine ; BUC(NO)2 ; S ; S&prime ; -dinitrosobucillamine ; BUC(NO)1 ; mononitrosobucillamine ; cGMP ; cyclic guanosine monophosphate ; DAF-2 ; 4 ; 5-diaminofluorescein ; DAF-2 DA ; 4 ; 5-diaminofluorescein diacetate ; DAN ; 2 ; 3-diaminonaphthalene ; DSC ; differential scanning calorimetry ; ESI ; electrospray ionization ; FT-IR ; Fourier transform infrared ; GSNO ; S-nitrosoglutathione ; HPLC ; high-performance liquid chromatography ; l-AT ; l-amino acid transport ; MS ; mass spectrometry
• 刊名：European Journal of Pharmacology
• 出版年：5 May, 2014
• 年：2014
• 卷：730
• 期：Complete
• 页码：171-179
• 全文大小：764 K

文摘

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鈥?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), ¹H nuclear magnetic resonance (¹H 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卤0.1) was more potent in vasorelaxation than NACNO (pD₂=6.4卤0.2), SNAP (pD₂=6.7卤0.1) and the mixture of SNAP plus NACNO (pD₂=6.7卤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卤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.