H2O2 increases production of constrictor prostaglandins in smooth muscle leading to enhanced arteriolar tone in Type 2 diabetic mice

Nóra Erdei, Zsolt Bagi, István Édes, Gabor Kaley, Akos Koller

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Abstract

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.

Original languageEnglish
Pages (from-to)H649-H656
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number1
DOIs
Publication statusPublished - Jan 1 2007

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Keywords

  • 3-nitrotyrosine
  • Arteriolar tone
  • Cyclooxygenase 2
  • Thromboxane A
  • db/db

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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