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Effects of superoxide anion generators and thiol modulators on nitrergic transmission and relaxation to exogenous nitric oxide in the sheep urethra
Author(s) -
GarciaPascual A,
Labadia A,
Costa G,
Triguero D
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703000
Subject(s) - chemistry , nitric oxide , superoxide , xanthine oxidase , stimulation , superoxide dismutase , dithiothreitol , soluble guanylyl cyclase , xanthine , medicine , endocrinology , biochemistry , biophysics , pharmacology , oxidative stress , enzyme , guanylate cyclase , organic chemistry , biology
The effects of superoxide anion generators, the nitric oxide (NO) scavenger 2‐(4‐carboxyphenyl)‐4,4,5,5‐tetramethylimidazoine‐1‐oxyl 3‐oxide (carboxy‐PTIO), the specific guanylate cyclase inhibitor 1H‐[1,2,4]‐oxadiazole‐[4,3‐a]‐quinoxalin‐1‐one (ODQ), and thiol modulating agents were investigated on relaxations induced by nitrergic stimulation and exogenous NO addition in the sheep urethra. Methylene blue (MB, 10 μ M ), pyrogallol (0.1 m M ) and xanthine (X, 0.1 m M )/xanthine oxidase (XO, 0.1 u ml −1 ) inhibited NO‐mediated relaxations, without affecting those induced by nitrergic stimulation. This resistance was not diminished following inhibition of endogenous Cu/Zn superoxide dismutase (Cu/Zn SOD) with diethyldithiocarbamic acid (DETCA, 3 m M ), which almost abolished tissue SOD activity. Carboxy‐PTIO (0.1–0.5 m M ) inhibited NO‐mediated relaxations but had no effect on responses to nitrergic stimulation, which were not changed by treatment with ascorbate oxidase (2 u ml −1 ). Relaxations to NO were reduced, but not abolished, by ODQ (10 μ M ), while nitrergic responses were completely blocked. The thiol modulators, ethacrynic acid (0.1 m M ), diamide (1.5 m M ), or 5,5′‐dithio‐bis (2‐nitrobenzoic acid) (DTNB, 0.5 m M ), and subsequent treatment with dithiothreitol (DTT, 2 m M ) had no effect on responses to nitrergic stimulation or NO. In contrast, N‐ethylmaleimide (NEM, 0.2 m M ) markedly inhibited both relaxations. L‐cysteine (L‐cys, 0.1 m M ) had no effect on responses to NO, while it inhibited those to nitrergic stimulation, in a Cu/Zn SOD‐independent manner. Our results do not support the view that the urethral nitrergic transmitter is free NO, and the possibility that another compound is acting as mediator still remains open.British Journal of Pharmacology (2000) 129 , 53–62; doi: 10.1038/sj.bjp.0703000