Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract only
Publication Acceptance Date: 12/10/2000
Publication Date: 3/7/2001
Citation: Gobejishvili, L., Saari, J.T., Adeagbo, A.S.O., Schuschke, D.A. 2001. Dietary copper deficiency increases INOS-mediated vascular relaxation in rat aorta [abstract]. The Federation of American Societies for Experimental Biology Journal. 15:A272. Interpretive Summary:
Technical Abstract: The attenuation of endothelium-dependent nitric oxide (NO)-mediated vasodilation is a consistent finding during copper-deficiency. However, there is often no effect on systemic blood pressure in experimental animals which suggest that peripheral vascular resistance is not altered. We hypothesize 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. In the current study, we used endothelium-denuded rat aortic rings to examine the role of iNOS in the regulation of vascular reactivity during dietary copper deficiency. Male weaning 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 dismutase (SOD), which preserves basal NO. Time to 50% relaxation in response to either compound was significantly shorter in the CuD than in CuA aortas. The maximal relaxation response to L-arginine was blocked by the iNOS inhibitor L-NIL and the relation to Cu,Zn-SOD was blocked by the No- sensitive guanylate cyclase inhibitor ODQ. Maximal activation of iNOS expression with LPS pretreatment did not cause a difference in vascular relaxation to L-arginine between dietary groups. Expression of the iNOS protein in the aortas was also not different between groups. These results suggest that while there is no apparent increase in protein expression, copper deficiency increases baseline iNOS activity in the vascular wall. Supported by NIH DK55030-02.