Pivotal role of Cu,Zn-superoxide dismutase in endothelium-dependent hyperpolarization
J. Clin. Invest. Keiko Morikawa, et al. 112:1871 doi:10.1172/JCI19351 [Go to this article.]

Figure 2
Reduced EDHF-mediated relaxations in Cu,Zn-SOD^–/– mice. Endothelium-dependent relaxations of mesenteric arteries from control WT mice (a) and from Cu,Zn-SOD^–/– mice (b) (n = 7 each) are shown. Indo, indomethacin (10^–5 M); L-NNA, 10^-4 M; KCl, 40–60 mM. In mesenteric arteries of control mice (a), endothelium-dependent relaxations were resistant to indomethacin or L-NNA, whereas in those of Cu,Zn-SOD^–/– mice (b), indomethacin and L-NNA markedly inhibited the relaxations. **P < 0.01, ***P < 0.0001. (c) Relative contribution of prostacyclin (PGI₂), NO, and EDHF to the endothelium-dependent relaxations of mesenteric arteries in response to ACh. In mesenteric arteries from Cu,Zn-SOD^–/– mice, EDHF-mediated relaxations were significantly attenuated and NO-mediated relaxations were significantly enhanced. **P < 0.01, ***P < 0.0001 vs. WT. (d and e) Inhibitory effect of the combination of charybdotoxin (CTx) and apamin (Apm) on EDHF-mediated relaxations. The combination significantly inhibited EDHF-mediated relaxations in both strains. ^#P < 0.0001. (f) Relative contribution of EDHF to the endothelium-dependent relaxations of mesenteric arteries as evaluated by the inhibitory effects of charybdotoxin and apamin. EDHF-mediated relaxations were also significantly reduced in Cu,Zn-SOD^–/– mice. ^##P < 0.01.