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ORIGINAL RESEARCH ARTICLE

Reducing Arginase Activity via Dietary Manganese Deficiency Enhances Endothelium-Dependent Vasorelaxation of Rat Aorta

Jodi L. Ensunsa^*, J. David Symons^,1, Louise Lanoue^*, Heather R. Schrader^* and Carl L. Keen^*,

^* Department of Nutrition, University of California at Davis, Davis, California 95616; College of Health, University of Utah, Salt Lake City, Utah 84112; and Department of Internal Medicine, University of California at Davis, Davis, California 95616

To whom requests for reprints should be addressed at ¹ College of Health, University of Utah, 250 South 1850 East, Room 241, Salt Lake City, UT 84112. E-mail: j.david.symons{at}hsc.utah.edu

L-Arginine is a common substrate for the enzymes arginase and nitric oxide synthase (NOS). Acute inhibition of arginase enzyme activity improves endothelium-dependent vasorelaxation, presumably by increasing availability of substrate for NOS. Arginase is activated by manganese (Mn), and the consumption of a Mn-deficient (Mn–) diet can result in low arginase activity. We hypothesize that endothelium-dependent vasorelaxation is greater in rats fed Mn– versus Mn sufficient (Mn+) diets. Newly weaned rats fed Mn+ diets (0.5 µg Mn/g; n = 12) versus Mn+ diets (45 µg Mn/g; n = 12) for 44 ± 3 days had (i) lower liver and kidney Mn and arginase activity (P 0.05), (ii) higher plasma L-arginine (P 0.05), (iii) similar plasma and urine nitrate + nitrite, and (iv) similar staining for endothelial nitric oxide synthase in thoracic aorta. Vascular reactivity of thoracic aorta (~720 µm i.d.) and small coronary arteries (~110 µm i.d.) was evaluated using wire myographs. Acetylcholine (ACh; 10^–8–10^–4 M) produced greater (P 0.05) vasorelaxation in thoracic aorta from Mn– rats (e.g., maximal percent relaxation, 79 ± 7%) versus Mn + rats (e.g., maximal percent relaxation, 54 ± 9%) at 5 of 7 evaluated doses. Tension produced by NOS inhibition using N^G monomethyl- L-arginine (L-NMMA; 10^–3 M) and vasorelaxation evoked by (i) arginase inhibition using difluoromethylornithine (DFMO; 10^–7 M), (ii) ACh (10^–8–10^–4 M) in the presence of DFMO, and (iii) sodium nitroprusside (10^–9–10^–4 M) were unaffected by diet. No differences existed between groups concerning these responses in small coronary arteries. These findings support our hypothesis that endothelium-dependent vasorelaxation is greater in aortic segments from rats that consume Mn– versus Mn+ diets; however, responses from small coronary arteries were unaffected.

Key Words: nitric oxide • nitric oxide synthase • difluoromethylornithine • superoxide dismutase • nitrotyrosine

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				A. Z. Kalea, D. A. Schuschke, P. D. Harris, and D. J. Klimis-Zacas Cyclo-Oxygenase Inhibition Restores the Attenuated Vasodilation in Manganese-Deficient Rat Aorta J. Nutr., September 1, 2006; 136(9): 2302 - 2307. [Abstract] [Full Text] [PDF]