S-nitrosoglutathione (GSNO) involved in storage and transport of nitric oxide (•NO), plays an important role in vascular homeostasis. Breakdown of GSNO can be catalyzed by γ−glutamyltransferase (GGT). We investigated whether vascular GGT influences the vasorelaxant effect of GSNO in isolated rat aorta. Histochemical localization of GGT and its activity measurement were performed by using chromogenic substrates in sections and in aorta homogenates, respectively. The role of GGT in GSNO metabolism was evaluated by measuring GSNO consumption rate (absorbance decay at 334 nm), •NO release was visualized and quantified with the fluorescent probe 4,5-diaminofluorescein diacetate. The vasorelaxant effect of GSNO was assayed using isolated rat aortic rings (in the presence or absence of endothelium). In each experiment, the role of GGT was assessed using a γ-glutamyl acceptor, glycylglycine, and a non-competitive inhibitor of GGT, serine borate complex. Specific GGT activity was histochemically localized in the endothelium. Consumption of GSNO and release of free •NO decreased and increased in presence of serine borate complex and glycylglycine, respectively. In endothelium-intact aorta, half maximal effective concentration (EC50) for GSNO (3.2 ± 0.5.10-7 M) was increased in the presence of serine borate complex serine borate complex (1.6 ± 0.2.10-6 M) and decreased with glycylglycine (4.7 ± 0.9.10-8 M). In endothelium-denuded aorta, EC50 for GSNO alone increased to 2.3 ± 0.3.10-6 M, with no change in the presence of serine borate complex. These data demonstrate the important role of endothelial GGT activity in mediating the vasorelaxant effect of GSNO in rat aorta under physiological conditions. Because new therapeutics treatments based on GSNO are actually developed, this endothelium-dependent mechanism involved in the vascular effects of GSNO should be taken into account in a pharmacological perspective.
|Autori:||DAHBOUL F; LEROY P; MAGUIN GATE K; BOUDIER A; GAUCHER C; LIMINANA P; LARTAUD I; POMPELLA A; PERRIN-SARRADO C.|
|Titolo:||Endothelial gamma-glutamyltransferase contributes to the vasorelaxant effect of S-nitrosoglutathione in rat aorta|
|Anno del prodotto:||2012|
|Appare nelle tipologie:||1.1 Articolo in rivista|