Reducing arginase activity via dietary manganese deficiency enhances endothelium-dependent vasorelaxation of rat aorta

Jodi L. Ensunsa, J. David Symons, Louise Lanoue, Heather R. Schrader, Carl L Keen

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20 Scopus citations


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 pg 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 NG 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.

Original languageEnglish (US)
Pages (from-to)1143-1153
Number of pages11
JournalExperimental Biology and Medicine
Issue number11
StatePublished - Dec 2004


  • Difluoromethylornithine
  • Nitric oxide
  • Nitric oxide synthase
  • Nitrotyrosine
  • Superoxide dismutase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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