Title: Inhibition of copper/zinc superoxide dismutase impairs NO ⋅-mediated endothelium-dependent relaxations
Abstract: The superoxide anion ([Formula: see text]) appears to be an important modulator of nitric oxide (NO ⋅) bioavailability. The present study was designed to characterize the role of copper/zinc superoxide dismutase (Cu/Zn SOD) in endothelium-dependent relaxations. Cu/Zn SOD was inhibited with the Cu 2+ chelator diethyldithiocarbamic acid (DETCA). In isolated canine basilar arteries, DETCA (7.6 × 10 −3 M) inhibited total vascular SOD activity by 46% ( P < 0.0001, n = 6–8 dogs). DETCA (7.6 × 10 −3 M) significantly reduced relaxations to bradykinin and A-23187 ( P < 0.05, n = 7–11). The inhibitory effect of DETCA was abolished by the [Formula: see text]scavenger 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron; 9.4 × 10 −3 M; P < 0.05, n = 6–13). Tiron significantly potentiated the relaxations to bradykinin in control rings ( P < 0.05, n = 13), and the nitric oxide synthase inhibitor N ω -nitro-l-arginine methyl ester (l-NAME; 3 × 10 −4 M) abolished these relaxations ( P < 0.0001, n = 6). DETCA and Tiron had no effect on the relaxations to diethylamine-NONOate or forskolin ( P > 0.05, n = 6). Our results demonstrate that endothelium-dependent relaxations mediated by NO ⋅ are impaired after the inhibition of Cu/Zn SOD. Relaxations to bradykinin (but not A-23187) were significantly augmented by Tiron. Pharmacological scavenging of [Formula: see text]reverses the effect of Cu/Zn SOD inhibition.
Publication Year: 1999
Publication Date: 1999-03-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 48
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