Ensunsa Jodi L, Symons J David, Lanoue Louise, Schrader Heather R, Keen Carl L
Department of Nutrition, University of California at Davis, CA 95616, USA.
Exp Biol Med (Maywood). 2004 Dec;229(11):1143-53. doi: 10.1177/153537020422901109.
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.
L-精氨酸是精氨酸酶和一氧化氮合酶（NOS）的常见底物。急性抑制精氨酸酶活性可改善内皮依赖性血管舒张，这可能是通过增加NOS底物的可利用性来实现的。精氨酸酶由锰（Mn）激活，食用缺锰（Mn-）饮食会导致精氨酸酶活性降低。我们假设，与食用锰充足（Mn+）饮食的大鼠相比，食用Mn-饮食的大鼠内皮依赖性血管舒张作用更强。将刚断奶的大鼠分别喂食Mn+饮食（0.5微克锰/克；n = 12）和Mn-饮食（45微克锰/克；n = 12）44±3天，结果发现：（i）肝脏和肾脏中的锰及精氨酸酶活性较低（P≤0.05）；（ii）血浆L-精氨酸水平较高（P≤0.05）；（iii）血浆和尿液中的硝酸盐+亚硝酸盐水平相似；（iv）胸主动脉中内皮型一氧化氮合酶的染色相似。使用线肌动描记器评估胸主动脉（内径约720微米）和小冠状动脉（内径约110微米）的血管反应性。在7个评估剂量中的5个剂量下，乙酰胆碱（ACh；10-8 - 10-4 M）在Mn-大鼠胸主动脉中产生的血管舒张作用更强（P≤0.05）（例如，最大舒张百分比为79±7%），而在Mn+大鼠中则较弱（例如，最大舒张百分比为54±9%）。使用N(G)-单甲基-L-精氨酸（L-NMMA；10-3 M）抑制NOS所产生的张力，以及（i）使用二氟甲基鸟氨酸（DFMO；10-7 M）抑制精氨酸酶、（ii）在DFMO存在下使用ACh（10-8 - 10-4 M）以及（iii）使用硝普钠（10-9 - 10-4 M）所诱发的血管舒张不受饮食影响。在小冠状动脉中，这些反应在各组之间没有差异。这些发现支持了我们的假设，即与食用Mn+饮食的大鼠相比，食用Mn-饮食的大鼠主动脉段的内皮依赖性血管舒张作用更强；然而，小冠状动脉的反应不受影响。
