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United States Department of Agriculture

Agricultural Research Service

Title: Nitric Oxide and Cyclic Gmp Are Elevated in Hearts of Copper-Deficient Rats

Authors
item Saari, Jack
item DAHLEN, GWEN

Submitted to: Medical Science Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 27, 1998
Publication Date: N/A

Interpretive Summary: Nitric oxide is a naturally occurring chemical in the body that was initially found to regulate the contraction of smooth muscle around blood vessels, but is now known to have a variety of other functions. For instance, nitric oxide can impair the heart's ability to contract, thus reducing its ability to pump blood. Because prior studies have shown that hearts of copper-deficient rats have a reduced ability to contract, we hypothesized that nitric oxide is elevated in copper-deficient hearts. Measurement of nitric oxide in hearts of copper-deficient and copper- adequate rats revealed that copper deficiency elevated nitric oxide concentration. Nitric oxide often acts by stimulating an enzyme called guanylate cyclase to produce the chemical cyclic GMP, which may also depress heart contraction. We also found that cyclic GMP concentration was elevated in hearts of copper-deficient rats. These findings suggest that the depressed heart function caused by dietary copper deficiency may be caused by elevated concentrations of nitric oxide and/or cyclic GMP. This information will be useful to scientists and consumers interested in the role of trace element nutrition on the function of the cardiovascular system.

Technical Abstract: Contractile function is depressed in hearts of copper-deficient rats. Recent studies have shown that nitric oxide, via stimulation of cyclic GMP production, impairs cardiac contraction. We have examined the hypothesis that cardiac nitric oxide and cyclic GMP production are increased, which would provide a possible explanation for reduced contractile force in copper-deficient animals. In a two-by-two experimental design, male, weanling Sprague-Dawley rats were fed diets that were either copper- adequate (CuA. 6.3 ug Cu/g diet) or copper-deficient (CuD, <0.5 ug Cu/g diet) and given water with or without the nitric oxide synthase inhibitor L-NAME (0.7 g/L) for five weeks. Copper deficiency was confirmed by depressed organ copper concentration, the presence of anemia and enlarged hearts. Combined nitrate and nitrite concentrations (NOX), as measured by HPLC, were elevated in hearts and urine of copper-deficient rats. Cyclic GMP, measured by an enzyme immunoassay method, was elevated in hearts of copper-deficient rats. NOX concentrations in hearts and urine were depressed by chronic L-NAME treatment. These findings suggest that nitric oxide and cyclic GMP could contribute to the depressed cardiac contraction found in copper deficiency.

Last Modified: 9/29/2014
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