Submitted to: Microcirculation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/9/1995
Publication Date: N/A
Interpretive Summary: Blood vessels change their diameter by contraction and relaxation of the smooth muscle surrounding them. A major source of agents that contract and relax this smooth muscle is the endothelial cell layer that lines the blood vessel. Blood vessels of copper-deficient rats are less able to relax and dilate in response to chemicals that cause release of nitric oxide (a dilating agent) from endothelial cells. In the present study we found that the reduced dilator response of small blood vessels was reversed in the presence of a copper-dependent enzyme that destroys superoxide free radical, a damaging by-product of normal metabolism. This protective effect indicates that the reduced dilator response to nitric oxide is caused by destruction of nitric oxide by superoxide, the superoxide being in excess because of reduced activity of the copper-dependent enzyme. Because blood vessel diameter determines blood pressure, this finding may explain how copper deficiency leads to high blood pressure in rats and indicates that proper copper nutrition is necessary for maintenance of healthy blood vessels. This information will be useful to scientists and consumers interested in trace element nutrition of the cardiovascular system.
Technical Abstract: This study was designed to investigate the role of dietary copper in nitric oxide-mediated arteriolar dilation. Male, weanling Sprague-Dawley rats were fed a purified diet that was either copper-adequate (6.0 ug Cu/g diet) or copper-deficient (0.3 ug Cu/g diet) for a period of four wks. Each rat was anesthetized with pentobarbital and its cremaster muscle was positioned in a Krebs'-filled bath to which graded concentrations of vasoactive agents were added. In the first series, responses to norepinephrine (NE 10**-9 to 10**-6 M) and acetylcholine (ACH 10**-7 to 10**-4 M) were compared in third-order arterioles. Second, the dilator response to 10**-5 M ACH in the absence and presence of 240 U/ml Cu, Zn- superoxide dismutase (SOD) was determined. Third, arteriolar dilation was determined in response to NO-independent stimulation of soluble guanylate cyclase with hydrogen peroxide (10**-7 to 10**-5 M) and to dibutyryl cGMP (10**-6 to 10**-4 M), dibutyryl cAMP (10**-6 to 10**-4 M), and papaverine 10**-4 M). The arteriole constrictor response to NE and the dilator response to hydrogen peroxide, dibutyryl cGMP and cAMP and papaverine were not different between the dietary groups. Copper deficiency attenuated the ACH-induced dilation but the response was restored in the presence of SOD. The inactivation of cytosolic Cu, Zn-SOD by restriction of dietary copper results in the depression of NO-mediated vascular smooth muscle relaxation probably by interaction of NO with superoxide.