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Antioxidant protection of NO‐induced relaxations of the mouse anococcygeus against inhibition by superoxide anions, hydroquinone and carboxy‐PTIO
Author(s) -
Lilley Elliot,
Gibson Alan
Publication year - 1996
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 - 10.1111/j.1476-5381.1996.tb16004.x
Subject(s) - chemistry , xanthine oxidase , glutathione , superoxide dismutase , superoxide , nitric oxide , antioxidant , biochemistry , ascorbic acid , stimulation , pharmacology , enzyme , endocrinology , biology , food science , organic chemistry
1 The potential protective effect of several antioxidants [Cu/Zn superoxide dismutase (Cu/Zn SOD), ascorbate, reduced glutathione (GSH), and α‐tocopherol (α‐TOC)] on relaxations of the mouse anococcygeus muscle to nitric oxide (NO; 15 μ m ) and, where appropriate, nitrergic field stimulation (10 Hz; 10 s trains) was investigated. 2 The superoxide anion generating drug duroquinone (100 μ m ) reduced relaxations to exogenous NO by 54 ± 6%; this inhibition was partially reversed by Cu/Zn SOD (250 u ml −1 ), and by ascorbate (500 μ m ). Following inhibition of endogenous Cu/Zn SOD activity with diethyldithiocarbamate (DETCA), duroquinone (50 μ m ) also reduced relaxations to nitrergic field stimulation (by 53 ± 6%) and this effect was again reversed by Cu/Zn SOD and by ascorbate. Neither GSH (500 μ m ) nor α‐TOC (400 μ m ) afforded any protection against duroquinone. 3 Xanthine (20 mu ml −1 ):xanthine oxidase (100 μ m ) inhibited NO‐induced relaxations by 73 ± 14%, but had no effect on those to nitrergic field stimulation, even after DETCA treatment. The inhibition of exogenous NO was reduced by Cu/Zn SOD (250 u ml −1 ) and ascorbate (400 μ m ), but was unaffected by GSH or α‐TOC (both 400 μ m ). 4 Hydroquinone (100 μ m ) also inhibited relaxations to NO (by 52 ± 10%), but not nitrergic stimulation. In this case, however, the inhibition was reversed by GSH (5–100 μ m ) and ascorbate (100–400 μ m ), although Cu/Zn SOD and α‐TOC were ineffective. 5 2‐(4‐Carboxyphenyl)‐4,4,5,5,‐tetramethylimidazoline‐1‐oxyl‐3‐oxide (carboxy‐PTIO, 50 μ m ) inhibited NO‐induced relaxations by 50 ± 4%, but had no effect on nitrergic responses; the inhibition was reduced by ascorbate (2–200 μ m ) and α‐TOC (10–200 μ m ), but not by Cu/Zn SOD or GSH. 6 Hydroxocobalamin (5–1000 μ m ) inhibited, equally, relaxations to both NO (‐logIC 40 3.14 ± 0.33) and nitrergic stimulation (‐logIC 40 3.17 ± 0.22). 7 Thus, a number of physiological antioxidants protected NO from superoxide anions, and from direct NO‐scavengers. The possibility that the presence of these antioxidants within nitrergically‐innervated tissues might explain the lack of effect of the NO inhibitors on nerve‐induced relaxation, without the need to invoke a transmitter other than free radical NO, is discussed.