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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Dietary Prevention of Obesity-related Disease Research » Research » Publications at this Location » Publication #74576


item Saari, Jack

Submitted to: Journal of Inflammation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/15/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary: Dietary copper deficiency has been shown to exacerbate inflammatory responses such as tissue swelling and dilation of blood vessels. Endotoxin is a fragment of bacteria which, if it enters the blood stream, initiates inflammation. The purpose of this study was to examine the effect of copper deficiency on a component of endotoxin-induced inflammation, the dilatory response of small blood vessels. This effect was determined by microscopic observation of the cremaster muscle microcirculation of rats. Injection of endotoxin into the veins of copper-deficient rats caused a relatively greater dilation of small blood vessels than it did in copper-adequate rats. Chemical blockade of the pathways of potential molecular mediators of endotoxin action indicated that the enhanced dilatory response in copper-deficient rats is caused by an increase in production of or sensitivity to inflammatory mediators, including histamine. This information will be useful to scientists and consumers interested in trace element nutrition of the cardiovascular system.

Technical Abstract: We have previously reported an exaggerated response to mast cell-mediated inflammation in copper-deficient rats. In the current study we determined the microvascular reactivity to inflammatory stimuli by lipopolysaccharide (LPS) during dietary copper restriction. Male Sprague-Dawley rats were fed purified diets which were either copper-adequate (CuA, 6 ug Cu/g) or copper-deficient (CuD, 0.4 ug Cu/g) for 4 weeks. Rats were anesthetized before the cremaster muscle was prepared for in vivo television microscopy. Arteriolar diameters were measured and then 2.5 mg/kg LPS was injected i.p. In separate groups, animals were pretreated with the NO- synthase inhibitor L-NAME (2 x 10**-4 M), the cyclooxygenase ibuprofen (9.6 x 10**-5 M) or the histamine receptor antagonist diphenhydramine (DPH, 10**-6 M). LPS caused arteriolar dilation in both dietary groups with the response being significantly greater in the CuD group. Ibuprofen and DPH, but not L-NAME, each significantly reduced but did not block the dilation in the CuD group. Ibuprofen and DPH together blocked the dilation. These results suggest that dietary copper deficiency increases arteriolar dilation to LPS. The mechanism apparently to involves a greater response to arachidonic acid metabolites and histamine but not to NO.