Abstract 5520: Upregulation of Arginase I Reduces Nitric Oxide-mediated Coronary Arteriolar Dilation in Patients With Type 2 Diabetes
We hypothesized that increased expression of arginase I reduces nitric oxide (NO)-mediated coronary arteriolar dilations in patients with type 2 diabetes (2-DM). Arterioles were dissected from right atrial appendages from patients with (N=17) or without (N=14) 2-DM. Coronary arterioles (123±16 μm) were cannulated, pressurized (80 mmHg) and changes in diameter were measured with videomicroscopy. After spontaneous tone developed, acetylcholine (ACh, 1 nM-1 μM) elicited dilations of coronary arterioles from patients without 2-DM (max. 82±5%), whereas it induced constrictions of arterioles from 2-DM patients (−41±9%). Dilations to the NO donor sodium nitroprusside were not different in the two groups. Inhibition of NO synthesis with L-NAME reduced coronary dilations in subjects without 2-DM, but did not affect constrictions to ACh in 2-DM patients. In vitro application of L-arginine (3 mM, 30 mins) restored coronary dilations to ACh in 2-DM patients (from −40±9 to 39±6%). Expression of arginase I, as detected by Western immunoblots and immunohistochemistry, was significantly increased in coronary arterioles of 2-DM patients. In conclusion, this study is the first to show that in coronary arterioles of patients with 2-DM arginase I expression is enhanced, which diminishes NO-mediated arteriolar dilation. Our findings allow for the feasibility that L-arginine supplementation may improve coronary endothelial function in patients with type 2 diabetes.Grants: AHA 0735540T and NIH NHLBI 43023.
This research has received full or partial funding support from the American Heart Association, Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).