Dietary copper deficiency increases inducible nitric oxide synthase-mediated vascular dilation in rat aorta

Authors

  • Leila Gobejishvili,

    1. Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky
    2. Microcirculation Research Center, I. Beritashvili Institute of Physiology, Tbilisi 380060, Republic of Georgia
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  • Jack T. Saari,

    1. U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota
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  • Ayotunde S.O. Adeagbo,

    1. Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky
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  • Xiaodong Zhang,

    1. Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky
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  • Dale A. Schuschke

    Corresponding author
    1. Department of Physiology and Biophysics, University of Louisville, Louisville, Kentucky
    • Department of Physiology and Biophysics, Health Sciences Center A1115, University of Louisville, Louisville, KY 40292. Phone: (502) 852–7553, FAX: (502) 852–6239
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  • The U.S. Department of Agriculture, Agricultural Research Service, Northern Plains Area, is an equal opportunity/affirmative action employer and all agency services are available without discrimination.

    Mention of trademark or proprietary product does not constitute a guarantee or warranty of the product by the U.S. Department of Agriculture and does not imply its approval to the exclusion of the other products that may be suitable.

    This article is a U.S. Government work and, as such, is in the public domain in the United States of America

Abstract

The attenuation of endothelium-dependent nitric oxide (NO)-mediated vasodilation is a consistent finding in both conduit and resistance vessels during copper deficiency. However, there is often no effect on systemic blood pressure in experimental animals, suggesting that peripheral vascular resistance is not altered. We hypothesized that baseline vascular smooth muscle relaxation may be maintained by a chronic increase in inducible NO synthase (iNOS) expression, as has been documented in hearts of copper-deficient rats. We used endothelium-denuded rat aortic rings to examine the role of iNOS in the regulation of vascular reactivity during dietary copper deficiency. Male weanling rats were fed a copper-adequate (CuA, 5.6 mg Cu/kg diet) or copper-deficient diet (CuD, 0.33 mg Cu/kg diet) for 4 weeks. The induction of “functional” iNOS was indicated by a relaxation response to the NO precursor L-arginine or to Cu,Zn-superoxide dismutase (SOD), which preserves basal NO. Time to 50% relaxation in response to either compound was significantly shorter in the CuD than in the CuA aortas. The maximal relaxation response to L-arginine was blocked by the iNOS inhibitor L-NIL, and the relaxation response to Cu,Zn-SOD was blocked by the NO-sensitive guanylate cyclase inhibitor ODQ. Maximal activation of iNOS expression with lipopolysaccharide pretreatment did not cause a difference in vascular relaxation between dietary groups in response to L-arginine. Expression of the iNOS protein in the aortas was also not different between groups. These results suggest that although there is no apparent increase in protein expression, copper deficiency increases baseline iNOS activity in the vascular wall. J. Trace Elem. Exp. Med. 15:85–95, 2002. © 2002 Wiley-Liss, Inc.

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