Hr. Kim et al., The effects of thiol compounds and ebselen on nitric oxide activity in rataortic vascular responses, J AUT PHARM, 21(1), 2001, pp. 23-28
1 Thiols have been implicated to play a role in a variety of aspects of nit
ric oxide (NO) generation and activity. Thiol dependence of nitric oxide sy
nthase (NOS) has remained controversial and its mechanism is not clear. Thi
s study investigates possible mechanisms between thiol (SH group) and NOS a
ctivation, through thiol compounds (glutathione, dithiothreitol, N-acetyl-L
-cysteine) and Ebselen [2-phenyl-1,2-benzisoselenazole-3 (2H)-one] on rat a
ortic vascular responses.
2 In rat thoracic aorta, acetylcholine (10(-6)-10(-9) M) induced a relaxati
on of phenylephrine (PE) (10(-7) M)-induced tone, which was inhibited dose
dependently by increasing concentration of ebselen (1-10 muM).
3 In rings of rat thoracic aorta, ebselen and NOS inhibitors (N-G-monomethy
l-L-arginine, N-G-nitro-L-arginine methyl ester) produced an augmentation o
f phenylephrine (10(-7) M)-induced tone and acety]choline induced a relaxat
ion of PE (10-7 M)-induced tone in rat thoracic aorta, which was inhibited
by ebselen (10 muM) like NOS inhibitor.
4 The thiol compounds (glutathione, dithiothreitol, and N-acetyl-L-cysteine
) alone did not change vascular tone in rat thoracic aorta. Pretreatment wi
th thiol compounds before ebselen treatment, however, reversed the inhibito
ry effect of ebselen which acts like the NOS inhibitor in rat thoracic aort
a. Posttreatment with thiol compounds after ebselen treatment did not rever
se the inhibitory effect of ebselen by as much as pretreatment.
5 Calcium ionophore A23187 (10(-7) M)-induced vasodilation was inhibited in
ebselen pretreated rat thoracic aorta, but sodium nitroprusside (SNP, 10(-
7) M)-induced relaxation was not inhibited by ebselen. This suggests that N
OS is involved in the inhibitory effect of ebselen on rat thoracic aorta re
laxation.
6 These results suggest that ebselen exerts an inhibitory action on the nit
ric oxide synthesis in rat thoracic aorta by interacting with thiol groups.