title: Copper deficiency alters vasodilation in the rat cremaster muscle microcirculation.
abstract: The effects of copper deficiency on smooth muscle relaxation were studied in the cremaster muscle microcirculation. Male Sprague-Dawley rats were fed either a copper-adequate diet (CuA, 5 micrograms copper/g diet) or copper-deficient diet (CuD, no added copper) for 17-27 d before experimentation. In vivo television microscopy was used to quantify agonist-induced diameter changes in third-order arterioles. Endothelium-dependent relaxation, which is hypothesized to be mediated by nitric oxide, was attenuated by copper deficiency. Both receptor (acetylcholine, 10(-7) to 10(-4) mol/L) and nonreceptor (calcium ionophore A23187, 10(-8) to 10(-7) mol/L) relaxation was decreased. Nitric oxide-mediated dilation, which was endothelium-independent (10(-7) to 10(-5) mol/L sodium nitroprusside), was also attenuated by copper deficiency. Maximal responses were as follows: for acetylcholine, 136 +/- 16% CuA vs. 45 +/- 15% CuD; for A23187, 104 +/- 16% CuA vs. 21 +/- 11% CuD; and for nitroprusside, 125 +/- 12% CuA vs. 46 +/- 13% CuD. There was no difference in microvascular dilation between groups treated with 10(-6) to 10(-4) mol/L of the phosphodiesterase inhibitor papaverine (e.g., CuA 109 +/- 11% vs. CuD 133 +/- 21% with 10(-4) mol/L). These results suggest that copper deficiency inhibits the nitric oxide-mediated mechanism of vascular smooth muscle relaxation without altering the capacity of the smooth muscle to relax. We suggest that copper deficiency either decreases nitric oxide radical availability or disrupts the nitric oxide-guanylate cyclase interaction.
authors.affiliation: Department of Physiology and Biophysics, University of Louisville, KY 40292.
authors.forename: D A
authors.initials: DA
authors.lastname: Schuschke
authors.forename: M W
authors.initials: MW
authors.lastname: Reed
authors.forename: J T
authors.initials: JT
authors.lastname: Saari
authors.forename: F N
authors.initials: FN
authors.lastname: Miller
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000284:Administration, Oral; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D003300:Copper / Q000008:administration & dosage / Q000172:deficiency*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000098:blood supply / Q000187:drug effects*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009599:Nitroprusside; D000001:Calcimycin; D003300:Copper; D000109:Acetylcholine