Reducing arginase activity via dietary manganese deficiency enhances endothelium-dependent vasorelaxation of rat aorta.
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 microg Mn/g; n = 12) versus Mn+ diets (45 microg Mn/g; n = 12) for 44 +/- 3 days had (i) lower liver and kidney Mn and arginase activity (P < or = 0.05), (ii) higher plasma L-arginine (P < or = 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 (approximately 720 microm i.d.) and small coronary arteries (approximately 110 microm i.d.) was evaluated using wire myographs. Acetylcholine (ACh; 10(-8)-10(-4) M) produced greater (P < or = 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.
Ensunsa
Jodi L
JL
Department of Nutrition, University of California at Davis, CA 95616, USA.
Symons
J David
JD
Lanoue
Louise
L
Schrader
Heather R
HR
Keen
Carl L
CL
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology; D001119:Arginase / Q000378:metabolism*; D001120:Arginine / Q000097:blood / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology; D004032:Diet; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D008345:Manganese / Q000172:deficiency*; D009566:Nitrates / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000378:metabolism; D009573:Nitrites / Q000032:analysis; D051381:Rats; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D009566:Nitrates; D009573:Nitrites; D008345:Manganese; D001120:Arginine; D019001:Nitric Oxide Synthase; D001119:Arginase