TY - JOUR
T1 - H2O2 increases production of constrictor prostaglandins in smooth muscle leading to enhanced arteriolar tone in Type 2 diabetic mice
AU - Erdei, Nóra
AU - Bagi, Zsolt
AU - Édes, István
AU - Kaley, Gabor
AU - Koller, Akos
PY - 2007/1
Y1 - 2007/1
N2 - Our previous study showed that arteriolar tone is enhanced in Type 2 diabetes mellitus (T2-DM) due to an increased level of constrictor prostaglandins. We hypothesized that, in mice with T2-DM, hydrogen peroxide (H2O2) is involved in the increased synthesis of constrictor prostaglandins, hence enhanced basal tone in skeletal muscle arterioles. Isolated, pressurized gracilis muscle arterioles (∼100 μm in diameter) of mice with T2-DM (C57BL/KsJ-db-/db-) exhibited greater basal tone to increases in intraluminal pressure (20-120 mmHg) than that of control vessels (at 80 mmHg, control: 25 ± 5%; db/db: 34 ± 4%, P < 0.05), which was reduced back to control level by catalase (db/db: 24 ± 4%). Correspondingly, in carotid arteries of db/db mice, the level of dichlorofluorescein-detectable and catalase-sensitive H2O 2 was significantly greater. In control arterioles, exogenous H 2O2 (0.1-100 μmol/l) elicited dilations (maximum, 58 ± 10%), whereas in arterioles of db/db mice H2O2 caused constrictions (-28 ± 8%), which were converted to dilations (maximum, 16 ± 5%) by the thromboxane A2/prostaglandin H 2 (TP) receptor antagonist SQ-29548. In addition, arteriolar constrictions in response to the TP receptor agonist U-46619 were not different between the two groups of vessels. Endothelium denudation did not significantly affect basal tone and H2O2-induced arteriolar responses in either control or db/db mice. Also, in arterioles of db/db mice, but not in controls, 3-nitrotyrosine staining was detected in the endothelial layer of vessels. Thus we propose that, in mice with T2-DM, arteriolar production of H2O2 is enhanced, which leads to increased synthesis of the constrictor prostaglandins thromboxane A2/prostaglandin H 2 in the smooth muscle cells, which enhance basal arteriolar tone. These alterations may contribute to disturbed regulation of skeletal muscle blood flow in Type 2 diabetes mellitus.
AB - Our previous study showed that arteriolar tone is enhanced in Type 2 diabetes mellitus (T2-DM) due to an increased level of constrictor prostaglandins. We hypothesized that, in mice with T2-DM, hydrogen peroxide (H2O2) is involved in the increased synthesis of constrictor prostaglandins, hence enhanced basal tone in skeletal muscle arterioles. Isolated, pressurized gracilis muscle arterioles (∼100 μm in diameter) of mice with T2-DM (C57BL/KsJ-db-/db-) exhibited greater basal tone to increases in intraluminal pressure (20-120 mmHg) than that of control vessels (at 80 mmHg, control: 25 ± 5%; db/db: 34 ± 4%, P < 0.05), which was reduced back to control level by catalase (db/db: 24 ± 4%). Correspondingly, in carotid arteries of db/db mice, the level of dichlorofluorescein-detectable and catalase-sensitive H2O 2 was significantly greater. In control arterioles, exogenous H 2O2 (0.1-100 μmol/l) elicited dilations (maximum, 58 ± 10%), whereas in arterioles of db/db mice H2O2 caused constrictions (-28 ± 8%), which were converted to dilations (maximum, 16 ± 5%) by the thromboxane A2/prostaglandin H 2 (TP) receptor antagonist SQ-29548. In addition, arteriolar constrictions in response to the TP receptor agonist U-46619 were not different between the two groups of vessels. Endothelium denudation did not significantly affect basal tone and H2O2-induced arteriolar responses in either control or db/db mice. Also, in arterioles of db/db mice, but not in controls, 3-nitrotyrosine staining was detected in the endothelial layer of vessels. Thus we propose that, in mice with T2-DM, arteriolar production of H2O2 is enhanced, which leads to increased synthesis of the constrictor prostaglandins thromboxane A2/prostaglandin H 2 in the smooth muscle cells, which enhance basal arteriolar tone. These alterations may contribute to disturbed regulation of skeletal muscle blood flow in Type 2 diabetes mellitus.
KW - 3-nitrotyrosine
KW - Arteriolar tone
KW - Cyclooxygenase 2
KW - Thromboxane A
KW - db/db
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U2 - 10.1152/ajpheart.00596.2006
DO - 10.1152/ajpheart.00596.2006
M3 - Article
C2 - 16997891
AN - SCOPUS:33846204372
SN - 0363-6135
VL - 292
SP - H649-H656
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 1
ER -