MICROVASCULAR CONTROL MECHANISMS IN COPPER DEFICIENCY

Dietary copper deficiency has long been associated with exaggerated in flammatory responses in both humans and experimental animals. However, the mechanisms for this increased response are not understood. By usi ng the rat cremaster muscle microcirculatory model as a window to the in vivo microcirculation, we have identified and studied three functio nal changes occurring in the microcirculation that operate during the inflammatory response and appear to be copper-dependent. First, we doc umented an increased postcapillary venule leakage of protein in respon se to histamine released by mass cells in copper-deficient rats. This response appears to be the result of increased numbers of mast cells a nd thereby increased available histamine. The second microvascular cha nge we noted in copper deficiency is that there is decreased in vivo t hrombogenesis with a resulting prolonged bleeding time. Additionally, in in vitro studies platelet-endothelial cell adhesion is diminished a nd the platelet concentration of the adhesion molecule von Willebrand Factor (vWF) is reduced. We propose that reduced vWF-mediated platelet adhesion accounts for the depressed thrombogenesis in copper deficien cy. The third difference we found is that nitric oxide-mediated arteri ole vasodilation is compromised, which may lead to increased periphera l vascular resistance. This functional deficit to NO can be reversed b y the addition of Cu, Zn-SOD. This suggests that it may result from in creased scavenging of NO by O-2(-) during copper deprivation. These ob servations demonstrate that dietary copper has several important funct ional roles in microvascular control mechanisms affecting inflammation , microhemostasis, and resistance to blood flow. (C) 1996 Wiley-Liss, Inc.