Author
SCHUSCHKE, DALE - UNIVERSITY OF LOUISVILLE | |
Saari, Jack |
Submitted to: Research Signpost: Research Developments in Agricultural and Food Chemistry
Publication Type: Review Article Publication Acceptance Date: 5/1/2000 Publication Date: 8/1/2000 Citation: Schuschke, D.A., Saari, J.T. 2000. Dietary copper deficiency impairs nitric oxide-mediated signal tranduction. Research Signpost: Research Developments in Agricultural and Food Chemistry. 3:65-70. Interpretive Summary: Technical Abstract: Dietary copper has an important role in the regulation of blood pressure through its effects on the contractile state of the vascular smooth muscle. By using the rat cremaster muscle microcirculatory model as a window to the in vivo microcirculation, we have shown that nitric oxide (NO)-mediated dilation is compromised in microvascular resistance vessels during dietary copper deficiency. This attenuated response can be reversed by the addition of Cu,Zn-SOD. Thus, we have proposed that the cuproenzyme Cu,Zn-SOD is inactivated by copper restriction allowing a buildup of superoxide anion (O2**-), which then reacts with NO to reduce the available NO for diffusion to the smooth muscle. This hypothesis is supported by the observation that an increase in peroxynitrite (ONOO**-), a product of the reaction between NO and O2**-, is concurrent with a decrease in Cu,Zn-SOD activity in copper-deficient rats. In addition to this direct effect of O2**- reducing the NO concentration, the subsequent ONOO**- may also reduce the synthesis of NO. Peroxynitrite is a known inhibitor of endothelial cell Ca**2+ mobilization, which is required for endothelial NO synthase activity, and we have shown that acetylcholine- induced Ca**2+ mobilization is reduced in arterioles of copper-deficient rats. The data therefore suggest that the inactivation of Cu,Zn-SOD by copper restriction results in the removal of available NO and in the inhibition of additional NO synthesis in endothelial cells. Further study of the in vivo microcirculation in rats suggests that attenuation of the NO-mediated dilation pathway occurs when liver copper concentrations fall below 5ug/g dry wt. as the result of feeding a diet with 1 ug Cu/g. |