Transgenic mice overexpressing Menkes ATPase, copper-transporting P-type ATPase (ATP7A; ATP7A Tg) rescued superoxide dismutase (SOD3) activity and endothelium-dependent relaxation in caveolin-1 knockout (KO) (Cav-1−/−) mice. A: protein levels of ATP7A, SOD3, SOD1, Cav-1, and actin in aortas from Cav-1 wild-type (WT) or Cav-1−/− double Tg mice overexpressing ATP7A were measured (n = 3). B: specific activity of SOD3 and SOD1 in tissue homogenates were assayed as described in Fig. 1. C: endothelium-dependent or -independent relaxation of mesenteric resistance arteries from Cav-1 WT or Cav-1−/− double Tg mice overexpressing ATP7A. Vasorelaxation was evoked by acetylcholine (ACh) and sodium nitroprusside (SNP) after preconstriction with phenylephrine (n = 6). D: membrane fractionation of mouse aorta of Cav-1 WT, Cav-1−/−, and ATP7A-Tg/Cav-1−/− mice. Equal amounts of caveolin-enriched lipid raft fractions (caveolae/lipid rafts; fraction 4 to 5) and non-caveolae/lipid rafts; fractions 10 to 13) from a pool of 4 mouse aortas were immunoblotted with antibodies as indicated. Results are presented as means ± SE. *P < 0.05. ATP7a, Menkes ATPase, copper-transporting P-type ATPase.