TY - JOUR
T1 - Arginase 1 contributes to diminished coronary arteriolar dilation in patients with diabetes
AU - Beleznai, Timea
AU - Feher, Attila
AU - Spielvogel, David
AU - Lansman, Steven L.
AU - Bagi, Zsolt
N1 - Funding Information:
K. H. is grateful for Ulysses support under JPL Contract 958056, and IPN3 support under NASA NAG 5-1560. D. H. acknowledges support from NASA through the CGRO guest investigator program. We also acknowledge the helpful comments of Chip Meegan, and the careful reading and constructive criticism of T. Kolatt and T. Piran.
PY - 2011/3
Y1 - 2011/3
N2 - 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 μM) 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 NG-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 NG-hydroxy-L-arginine (10 μM), 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.
AB - 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 μM) 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 NG-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 NG-hydroxy-L-arginine (10 μM), 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.
KW - Coronary microvessel
KW - Endothelial nitric oxide synthase
KW - Endothelium
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U2 - 10.1152/ajpheart.00831.2010
DO - 10.1152/ajpheart.00831.2010
M3 - Article
C2 - 21217072
AN - SCOPUS:79955075627
SN - 0363-6135
VL - 300
SP - H777-H783
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 3
ER -