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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 #95501
Title: ENDOTHELIAL CELL CALCIUM MOBILIZATION TO ACETHYLCHOLINE IS ATTENUATED IN COPPER-DEFICIENT RATS

Author
item SCHUSCHKE, D - UNIVERSITY OF LOUISVILLE
item FALCONE, J - UNIVERSITY OF LOUISVILLE
item Saari, Jack
item FLEMING, J - UNIVERSITY OF LOUISVILLE
item PERCIVAL, S - UNIV OF FLORIDA
item YOUNG, S - UNIVERSITY OF LOUISVILLE
item PASS, J - UNIVERSITY OF LOUISVILLE
item MILLER, F - UNIVERSITY OF LOUISVILLE

Submitted to: Endothelium
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/4/1999
Publication Date: N/A
Citation: N/A

Interpretive Summary: Changes in the diameter of blood vessels affect blood flow to the tissues they serve and also influence blood pressure. The ability of blood vessels to increase in diameter is impaired in dietary copper deficiency, which may reduce blood flow to tissues or cause high blood pressure. This reduced ability of blood vessels to increase their diameter is not well understood, but is thought to involve reduced production of, or interference with the action of, nitric oxide, a specific chemical that is produced in the blood vessel wall. We examined the enzyme that produces nitric oxide in blood vessels of rats and found that it was not altered in copper deficiency. Release of calcium within the cell is necessary to cause production of nitric oxide. When blood vessels were treated with a substance that causes them to increase in diameter we found that calcium release was greatly reduced by dietary copper deficiency and coincided with the reduced ability of blood vessels to increase in diameter. This is the first finding of an altered handling of calcium in copper deficiency. This study contributes to our knowledge of how dietary copper deficiency adversely affects heart and blood vessel function and may be relevant to our understanding of cardiovascular disease in general.

Technical Abstract: Dietary copper deficiency significantly attenuates NO-mediated vascular smooth muscle relaxation and vasodilation. There is evidence for both increased inactivation of the NO radical by superoxide anion and oxidative damage to the endothelium where NO is produced. The current study was designed to examine the NO synthetic pathway in the endothelium during copper deficiency. Male weanling rats were fed a copper-adequate (CuA, 6.4 mg Cu/kg diet) or copper-deficient (CuD, 0.4 mg Cu/kg diet) diet for four weeks. Cremasteric arterioles (~100 um diameter) were isolated and used for the experiments. Western blot analysis of the arteriole eNOS concentration did not demonstrate a difference between dietary groups. Acetylcholine (Ach)-induced vasodilation was significantly reduced in the CuD group both before and after pretreatment with the eNOS substrate L-arginine. Mobilization of endothelial intracellular calcium ([Ca**2+]i)stimulated by 10**-6M Ach was significantly inhibited in the arterioles from CuD rats. Coincident with the inhibition of [Ca**2+]i and vasodilation was a depression of vascular Cu/Zn-SOD activity. These data suggest that endothelial Ca**2+ signaling and agonist-stimulated NO-mediated vascular dilation are likely reduced by increased oxidative damage in copper-deficient rats.