The aim of the present study was to assess the role of superoxide anions in the relaxation induced by acetylcholine (ACh) in aortic segments from male rats, and to investigate if their production is altered by sex hormone deprivation. In segments precontracted with 10 nmol/l noradrenaline, ACh (0.1 nmol/–10 μmol/l) induced concentration-dependent relaxation, which was greater in segments from castrated compared with control animals. ACh-induced relaxation was abolished in segments from control rats, and reduced in those from castrated rats, by 0.1 mmol/l NG-nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthase inhibitor). Indomethacin (1 μmol/l; a cyclo-oxygenase blocker) decreased the ACh-induced relaxation in arteries from control males only. Incubation of segments with superoxide dismutase (SOD; 100 units/ml; a superoxide anion scavenger) enhanced and reduced relaxation in segments from control and castrated animals respectively. For arteries from castrated animals, the presence of SOD plus L-NAME abolished such responses. In these arteries, incubation with L-NAME abolished the relaxation caused by ACh when the segments were precontracted with 30 mmol/l KCl. In segments obtained from castrated rats and pretreated with L-NAME, 1 mmol/l tetraethylammonium or 0.4 μmol/l charybdotoxin [blockers of Ca2+-sensitive and large-conductance Ca2+-sensitive (BKCa) K+ channels respectively] abolished the relaxation induced by ACh. These results suggest that ACh generates endothelial NO and superoxide anions from the arterial wall in both control and castrated animals; these agents negatively modulate ACh-induced relaxation in control rats by destruction of NO, and positively modulate ACh-induced relaxation in castrated rats by activation of BKCa channels.
Androgen deprivation facilitates acetylcholine-induced relaxation by superoxide anion generation
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Mercedes FERRER, Nuria TEJERA, Jesús MARÍN, Gloria BALFAGÓN; Androgen deprivation facilitates acetylcholine-induced relaxation by superoxide anion generation. Clin Sci (Lond) 1 December 1999; 97 (6): 625–631. doi: https://doi.org/10.1042/cs0970625
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