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Diabetes induces endothelial dysfunction: role of eNOS uncoupling and arginase
Author(s) -
Thengchaisri Naris,
Hein Travis W.,
Kuo Lih
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.678.4
Subject(s) - enos , arginase , vasodilation , medicine , endocrinology , diabetes mellitus , sodium nitroprusside , streptozotocin , nitric oxide , endothelial dysfunction , serotonin , diabetic angiopathy , chemistry , arginine , nitric oxide synthase , biochemistry , receptor , amino acid
We studied the role of arginase and eNOS in vascular dysfunction using porcine diabetic model. Pigs (8‐wk old) were subjected to streptozotocin (STZ) injection for diabetes induction. Two weeks after STZ or saline (control) injections, coronary arterioles (50–100 μm) were isolated and pressurized for in vitro studies. The vasodilations to eNOS activators (flow and serotonin), but not to NO donor sodium nitroprusside, were significantly reduced in the diabetic group. Application of H 2 O 2 scavenger catalase (1,000 units/ml) did not alter the serotonin response in control or diabetic group but inhibited flow‐mediated dilation in vessels from the diabetic pigs. The inhibitory effect of catalase on flow‐mediated dilation was absent after extraluminal application of L‐arginine (3 mM). Furthermore, inhibition of NOS with L‐NAME (10 μM) completely abolished serotonin‐ and flow‐mediated dilations in both control and diabetic groups. Interestingly, treating the diabetic vessels with arginase inhibitor norNOHA (0.1 mM) improved the serotonin‐induced vasodilation to the same extent as by L‐arginine application. In conclusion, H 2 O 2 from the uncoupled eNOS serves as a vasodilatory mediator for flow‐induced dilation of diabetic porcine coronary arterioles. On the other hand, L‐arginine deficiency due to arginase upregulation contributes to the impaired coronary arteriolar dilation to serotonin in diabetes.