Abnormalities of endothelium-dependent responses in mesenteric arteries from Otsuka Long-Evans Tokushima Fatty (OLETF) rats are improved by chronic treatment with thromboxane A(2) synthase inhibitor

作者：Matsumoto Takayuki; Takaoka Eri; Ishida Keiko; Nakayama Naoaki; Noguchi Eri; Kobayashi Tsuneo; Kamata Katsuo^*

来源：Atherosclerosis, 2009, 205(1): 87-95.

DOI：10.1016/j.atherosclerosis.2008.11.015

• Diabetes
• EDCF
• EDHF
• Endothelial dysfunction
• Mesenteric artery
• Ozagrel

Thromboxane A(2) (TXA(2)) is thought to contribute to the development of diabetic complications. We tested the hypothesis that the impaired endothelial function seen in Otsuka Long-Evans Tokushima Fatty (OLETF) rats (a type 2 diabetic model) might be improved by chronic treatment with ozagrel, a TXA2 synthase inhibitor. in mesenteric arteries from OLETF rats (40-46 weeks old) [vs. those from age-matched Long-Evans Tokushima Otsuka (LETO) rats]: (1)ACh-induced endothelium-dependent relaxation, NO-mediated relaxation, and endothelium-derived hyperpolarizing factor (EDHF)-type relaxation were all reduced; (2) ACh-induced cyclooxygenase-dependent contraction was enhanced; (3) endothelium-derived contracting factor (EDCF)-mediated contraction was enhanced; (4) ACh-stimulated nitrite production was reduced but the nitrate/nitrite ratio was increased; and (5) ACh-stimulated production Of TXA2 Was increased. Chronic treatment with ozagrel (100 mg/kg/day for 4 weeks, starting when they were 36-42 weeks of age) partly corrected the above abnormalities. These results suggest that ozagrel has normalizing effects on endothelial functions in OLETF mesenteric arteries, at least partly by increasing endothelium-derived relaxing factors (i.e., NO and EDHF) signaling and reducing EDCF signaling.

• 出版日期2009-7
• 单位河北医科大学