Endothelial cell calcium mobilization to acetylcholine is attenuated in copper-deficient rats

Dietary copper deficiency significantly attenuates nitric oxide (NO)-mediat ed vascular smooth muscle relaxation and Vasodilation. There is evidence fo r both increased inactivation of the NO radical by superoxide anion, and ox idative damage to the endothelium where NO is produced. The current study w as designed to examine the NO synthetic pathway in the endothelium during c opper deficiency, Male weanling rats were fed a copper-adequate (CuA, 6.4 m g Cu/kg diet) or copper-deficient (CuD, 0.4 mg Cu/kg diet) diet for four we eks. Cremasteric arterioles (similar to 100 mu m diameter) were isolated an d used for the experiments. Western blot analysis of the arteriole endothel ial nitric oxide synthase (eNOS) concentration did not show a difference be tween dietary groups, Acetylcholine (Ach)-induced vasodilation was signific antly reduced in the CuD group both before and after pretreatment with the eNOS substrate L-arginine. Endothelial intracellular calcium ([Ca2+](i)) st imulated by 10(-6)M Ach was significantly inhibited in the arterioles from CuD rats. Coincident with the inhibition of [Ca2+](i) and vasodilation was a depression of vascular Cu/Zn-SOD activity and an increase in plasma perox ynitrite activity. These data suggest that endothelial Ca2+ signaling and a gonist-stimulated NO-mediated vascular dilation are likely reduced by incre ased oxidative damage in copper-deficient rats.