The effects of thiol compounds and ebselen on nitric oxide activity in rataortic vascular responses

Citation
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
Citations number
24
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF AUTONOMIC PHARMACOLOGY
ISSN journal
0144-1795 → ACNP
Volume
21
Issue
1
Year of publication
2001
Pages
23 - 28
Database
ISI
SICI code
0144-1795(200102)21:1<23:TEOTCA>2.0.ZU;2-9
Abstract
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.