CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 1, January/February 2011
AFRICA
7
Cardiovascular Topics
The vascular endothelium masks the persistent inhibition
of rat thoracic arterial tone induced by S-nitrosoglutathione
M SARR, FB SAR, L GUEYE, MO KANE, A WELE, AS DIALLO, V SCHINI-KERTH, B MULLER
Summary
Aim:
In endothelium-denuded arteries, the nitric oxide
(NO) donor S-nitrosoglutathione (GSNO) induced a persis-
tent 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 endothe-
lium, 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 nitro-
sothiol 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 N
w
-nitro-L-arginine
methylester (L-NAME) or in GSNO-denuded rings.
The relaxing effects of NAC were due to the mobilisa-
tion 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.
Keywords:
endothelium, nitric oxide, S-nitrosoglutathione
Submitted 29/7/09, accepted 10/3/10
Cardiovasc J Afr
2011;
22
: 7–13
Numerous
in vitro
and
in vivo
studies have demonstrated that in
vascular diseases, the ability of the endothelium to secrete NO
is reduced.
1-8
Therefore, endothelium-independent nitric oxide
donors might be useful to prevent or reverse endothelial dysfunc-
tion. Moreover, nitrosothiol (RSNO) formation from biotrans-
formation of NO donors can take part in the transnitrosation
reaction, which is a tranfer of bound NO from one thiol group to
another, that under appropriate conditions, can release NO.
9
NO
donors such as nitrosoglutathione (GSNO) have been developed
as valuable tools for experimental pharmacological studies and
probably will be used in the future to restore vascular protection in
pathological blood vessels,
10-12
or to prevent vascular dysfunction.
Furthermore, little data exist on nitrosylation of thiols in
healthy vascular tissue, and even less on functional consequences
of this phenomenon on vasomotor activity. Therefore, the
influence of endothelium on mechanisms through which nitric
oxide donors can contribute to the hypo-reactivity of contractile
agonists in healthy vessels is not well elucidated. This study was
an attempt to investigate the effect of GSNO in normal vessels
and to functionally characterise the underlying mechanism
whereby this nitric oxide donor enhanced arterial hypo-respon-
siveness and relaxation.
Methods
Experiments were conducted in accordance with the
Guide for
the Care and Use of Laboratory Animals
as adapted and promul-
gated by the US National Institutes of Health (agreement number
B 67900, given by French authorities). The thoracic aorta was
removed from male Wistar rats (12–14 weeks old, 300–380 g)
after anaesthesia with pentobarbital (60 mg/kg, i.p.) and cleaned
of connective tissue and fat in Krebs solution (composition in
mM: NaCl 119; KCl 4.7; MgSO
4
1.17; CaCl
2
1.25; KH
2
PO
4
1.18; NaHCO
3
25; glucose 11). The endothelium was removed
Laboratoire de Physiologie Pharmaceutique, Faculté de
Médecine et de Pharmacie, Dakar, Sénégal
M SARR, Pharm D, PhD,
AS DIALLO, Pharm D, PhD
FB SAR, MD, PhD
L GUEYE, MD, PhD
MO KANE, Pharm D, PhD
Unité Mixte Internationale (UMI – Environnement, Santé et
Sociétés), Université Cheikh Anta Diop, Dakar, Sénégal
M SARR, Pharm D, PhD
FB SAR, MD, PhD
L GUEYE, MD, PhD
CNRS UMR 7213, Biophotonique et Pharmacologie, Illkirch,
France
V SCHINI-KERTH, Pharm D, PhD
Pharmacologie, INSERM, Université Victor Segalen,
Bordeaux, France
B MULLER, Pharm D, PhD
Laboratorie de Chimie therapeutique, Faculté de Médecine
et Pharmacie, Dakar, Sénègal
A WELE, Pharm D, PhD
