A role for dietary copper in nitric oxide-mediated vasodilation.
OBJECTIVE
This study was designed to investigate the role of dietary copper in nitric oxide-mediated arteriolar dilation.


METHODS
Male weanling Sprague-Dawley rats were fed a purified diet that was either copper-adequate (6.0 micrograms Cu per g diet) or copper-deficient (0.3 microgram Cu per g diet) for a period of 4 weeks. 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)-10(-6) M) and acetylcholine (ACH 10(-7)-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)-10(-5) M) and to dibutyryl cGMP (10(-6)-10(-4) M), dibutyryl cAMP (10(-6)-10(-4) M), and papaverine (10(-4) M).


RESULTS
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.


CONCLUSIONS
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.
Schuschke
D A
DA
Center for Applied Microcirculatory Research, University of Louisville, Kentucky, USA.
Saari
J T
JT
Miller
F N
FN
D000818:Animals; D001160:Arterioles / Q000187:drug effects; D003300:Copper / Q000494:pharmacology*; D004032:Diet; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects*
D009569:Nitric Oxide; D003300:Copper; D013482:Superoxide Dismutase