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The vascular endothelium masks the persistent inhibition of rat thoracic arterial tone induced by S-nitrosoglutathione.

Aim: In endothelium-denuded arteries, the nitric oxide (NO) donor S-nitrosoglutathione (GSNO) induced a persistent hypo-reactivity to vasoconstrictors, and low-molecular weight thiols such as N-acetyl cysteine (NAC) produced a relaxant effect. These effects were attributed to the formation of vascular NO stores. In arteries with a functional endothelium, such long-lasting effects on arterial tone have not been well characterised. In this study, we proposed to examine the possibility of storing exogenous NO when the vascular endothelium is still able to produce its own NO. Methods: For this purpose, changes in isometric tension of isolated arteries were assessed in organ chambers, and nitrosothiol formation was characterised by confocal microscopy. Results: In rat aortic rings with endothelium pre-exposed to GSNO, the contractile response to norepinephrine (NE) was not attenuated in comparison with control rings, but NAC induced a relaxant effect. However, an attenuation of the response to NE was observed in GSNO-exposed, intact aortic rings after inhibition of NO synthase by Nw-nitro-L-arginine methylester (L-NAME) or in GSNO-denuded rings. The relaxing effects of NAC were due to the mobilisation of NO from nitrosothiols after nitrosylation of protein SH residues. Moreover, the hypo-reactivity to NE and the relaxant effect of NAC were abolished by 1H-[1,2,4] oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), an inhibitor of soluble guanylyl cyclase, and partially by the K+-sensitive channel inhibitor tetra-ethyl-ammonium (TEA). Conclusion: These data show that endothelium-derived NO masked the persistent effect of GSNO in rat thoracic aorta. However, the ability of GSNO to form releasable NO stores without altering the vascular tone can be particularly useful in preventing endothelial dysfunction in which NO formation decreases.


Auteur(s) : M SARR, FB SAR, L GUEYE, MO KANE, A WELE, AS DIALLO, V SCHINI-KERTH, B MULLER.
Pages : 7-13
Année de publication : 2011
Revue : Cardiovascular Journal of africa
N° de volume : 22
Type : Article
Mise en ligne par : KANE Modou Oumy