The superoxide anion (O₂·) 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 Cu²⁺ chelator diethyldithiocarbamic acid (DETCA). In isolated canine basilar arteries, DETCA (7.6 × 10³ M) inhibited total vascular SOD activity by 46% (P < 0.0001, n = 6-8 dogs). DETCA (7.6 × 10³ M) significantly reduced relaxations to bradykinin and A-23187 (P < 0.05, n = 7-11). The inhibitory effect of DETCA was abolished by the O₂· scavenger 4,5-dihydroxy-1,3-benzenedisulfonic acid (Tiron; 9.4 × 10³ 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-nitro-L-arginine methyl ester (L-NAME; 3 × 10⁴ 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 O₂· reverses the effect of Cu/Zn SOD inhibition.

A-23187; bradykinin; cerebral vessels; inflammation; Tiron

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