Arginase 1 contributes to diminished coronary arteriolar dilation in patients with diabetes

被引:74
作者
Beleznai, Timea [2 ,3 ]
Feher, Attila [1 ,3 ]
Spielvogel, David [4 ]
Lansman, Steven L. [4 ]
Bagi, Zsolt [1 ,2 ]
机构
[1] New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA
[2] Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England
[3] Univ Debrecen, Inst Cardiol, Div Clin Physiol, Debrecen, Hungary
[4] New York Med Coll, Dept Cardiothorac Surg, Valhalla, NY 10595 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2011年 / 300卷 / 03期
关键词
coronary microvessel; endothelium; endothelial nitric oxide synthase; ENDOTHELIUM-DEPENDENT VASODILATION; NITRIC-OXIDE SYNTHASE; L-ARGININE; HIGH-FAT; MEDIATED DILATION; HEALTHY-SUBJECTS; VITAMIN-E; NO; DYSFUNCTION; MELLITUS;
D O I
10.1152/ajpheart.00831.2010
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Beleznai T, Feher A, Spielvogel D, Lansman SL, Bagi Z. Arginase 1 contributes to diminished coronary arteriolar dilation in patients with diabetes. Am J Physiol Heart Circ Physiol 300: H777-H783, 2011. First published January 7, 2011; doi:10.1152/ajpheart.00831.2010.-Arginase 1, via competing with nitric oxide (NO) synthase for the substrate L-arginine, may interfere with NO-mediated vascular responses. We tested the hypothesis that arginase 1 contributes to coronary vasomotor dysfunction in patients with diabetes mellitus (DM). Coronary arterioles were dissected from the right atrial appendages of 41 consecutive patients with or without DM (the 2 groups suffered from similar comorbidities), and agonist-induced changes in diameter were measured with videomicroscopy. We found that the endothelium-dependent agonist ACh elicited a diminished vasodilation and caused constriction to the highest ACh concentration (0.1 mu M) with a similar magnitude in patients with (18 +/- 8%) and without (17 +/- 9%) DM. Responses to ACh were not significantly affected by the inhibition of NO synthesis with N-G-nitro-L-arginine methyl ester in either group. The NO donor sodium nitroprusside-dependent dilations were not different in patients with or without DM. Interestingly, we found that the presence of N-G-hydroxy-L-arginine (10 mu M), a selective inhibitor of arginase or application of L-arginine (3 mM), restored ACh-induced coronary dilations only in patients with DM (to 47 +/- 6% and to 40 +/- 19%, respectively) but not in subjects without DM. Correspondingly, the protein expression of arginase 1 was increased in coronary arterioles of patients with DM compared with subjects without diabetes. Moreover, using immunocytochemistry, we detected an abundant immunostaining of arginase 1 in coronary endothelial cells of patients with DM, which was colocalized with NO synthase. Collectively, we provided evidence for a distinct upregulation of arginase 1 in coronary arterioles of patients with DM, which contributes to a reduced NO production and consequently diminished vasodilation.
引用
收藏
页码:H777 / H783
页数:7
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