Abstract
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 language | English (US) |
|---|---|
| Pages (from-to) | 1143-1153 |
| Number of pages | 11 |
| Journal | Experimental Biology and Medicine |
| Volume | 229 |
| Issue number | 11 |
| State | Published - Dec 2004 |
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Keywords
- Difluoromethylornithine
- Nitric oxide
- Nitric oxide synthase
- Nitrotyrosine
- Superoxide dismutase
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Reducing arginase activity via dietary manganese deficiency enhances endothelium-dependent vasorelaxation of rat aorta. / Ensunsa, Jodi L.; Symons, J. David; Lanoue, Louise; Schrader, Heather R.; Keen, Carl L.
In: Experimental Biology and Medicine, Vol. 229, No. 11, 12.2004, p. 1143-1153.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reducing arginase activity via dietary manganese deficiency enhances endothelium-dependent vasorelaxation of rat aorta
AU - Ensunsa, Jodi L.
AU - Symons, J. David
AU - Lanoue, Louise
AU - Schrader, Heather R.
AU - Keen, Carl L
PY - 2004/12
Y1 - 2004/12
N2 - 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.
AB - 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.
KW - Difluoromethylornithine
KW - Nitric oxide
KW - Nitric oxide synthase
KW - Nitrotyrosine
KW - Superoxide dismutase
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UR - http://www.scopus.com/inward/citedby.url?scp=10044233909&partnerID=8YFLogxK
M3 - Article
C2 - 15564441
AN - SCOPUS:10044233909
VL - 229
SP - 1143
EP - 1153
JO - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)
JF - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)
SN - 1535-3702
IS - 11
ER -