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Departments of Anesthesiology and Pharmacology, Mayo Clinic, Rochester, Minnesota 55905
The superoxide anion
(O
2·) 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 × 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 O
2·
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
-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 O
2·
reverses the effect of Cu/Zn SOD inhibition.
A-23187; bradykinin; cerebral vessels; inflammation; Tiron
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