期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 683, 期 1-3, 页码 217-225出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2012.03.022
关键词
Complications; Diabetes; Hyperglycemia; Microvasculature; Vascular smooth muscle
资金
- MEXT (Ministry of Education, Culture, Sports, Science and Technology) in Japan [21590290]
- MEXT [05H007]
- Grants-in-Aid for Scientific Research [21590290] Funding Source: KAKEN
Diabetic complications are associated with small artery dysfunctions. The objective of this study was to identify differences in endothelial cell-denuded mesenteric artery second branch (mesenteric artery-2) contraction, as a typical small artery, between diabetic and non-diabetic mice. Contractile responses in mesenteric artery-2 were assessed in male type 2 diabetic ob/ob mice aged 16-22 weeks and in age-matched control (Lean) mice. Phenylephrine induced dose-dependent contractions in Lean mice (1126.8 +/- 28.6 mN/mm tissue at 10 mu M phenylephrine; n=5), which were significantly reduced in ob/ob mice (716.8 +/- 40.8 mN/mm at 10 mu M phenylephrine; n=5). Exposure to high glucose (HG; twice the normal glucose [NG] concentration) enhanced phenylephrine-induced contraction in Lean (1341.4 +/- 15.5 mN/mm; n=5) but not in ob/ob mice. These dysfunctions did not involve alpha(1)-receptor sensitization or protein kinase activity, although the calcium sensitivity of contraction was decreased in ob/ob mice. The Rho kinase inhibitor Y27632 suppressed the difference between Lean and ob/ob mice under NG conditions, which was accompanied by Rho A inactivation. Under HG conditions, glucose-dependent Rho A activation persisted in ob/ob mice whereas Rho kinase expression was reduced. These data suggest that inactivation of Rho A reduced contractibility under NG conditions, and the lack of glucose dependency is associated with reduced Rho kinase expression. (C) 2012 Elsevier B. V. All rights reserved.
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