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
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