ELEVATED GLUCOSE PROMOTES GENERATION OF ENDOTHELIUM-DERIVED VASOCONSTRICTOR PROSTANOIDS IN RABBIT AORTA
ELEVATED GLUCOSE PROMOTES GENERATION OF ENDOTHELIUM-DERIVED VASOCONSTRICTOR PROSTANOIDS IN RABBIT AORTA
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DOI：
10.1172/jci114521
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发表时间：
1990-03-01
影响因子：
15.9
通讯作者：
COHEN, RA
中科院分区：
文献类型：
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作者：
TESFAMARIAM, B;BROWN, ML;COHEN, RA
葡萄糖对内皮依赖性反应和血管活性前列腺素类产生的影响通过在对照（5.5或11 mM）或升高的（44 mM）葡萄糖中孵育分离的兔前列腺6小时来确定，以模拟正常血糖和高血糖条件。葡萄糖浓度升高，收缩次最大程度的苯乙醯胺孵育的环的血管内皮依赖性舒张乙酰胆碱诱导的血管内皮依赖性舒张与对照葡萄糖孵育相比，表现出显着下降。吲哚美辛，环氧合酶抑制剂，或SQ 29548，前列腺素H2/血栓烷A2受体拮抗剂，治疗，恢复乙酰胆碱松弛环在葡萄糖升高到正常，而这些药物对控制葡萄糖孵育环的松弛没有影响。用甘露糖（44 mM）孵育的主动脉作为高渗对照，正常松弛至乙酰胆碱。A23187和硝普钠引起的舒张反应在对照组和高糖组之间没有差异。放射免疫测定显示乙酰胆碱刺激的血栓素A2和前列腺素F2 α的释放显著增加。在有内皮细胞但无内皮细胞的大鼠中，与升高的葡萄糖孵育，但与对照葡萄糖孵育。因此，糖尿病内皮功能障碍的一个可能机制是高血糖诱导的内皮源性血管收缩剂前列腺素类的产生增加。
The effects of glucose on endothelium-dependent responses and vasoactive prostanoid production were determined by incubating isolated rabbit aortae in control (5.5 or 11 mM) or elevated (44 mM) glucose for 6 h to mimic euglycemic and hyperglycemic conditions. Rings of aortae incubated in elevated glucose, contracted submaximally by phenylephrine, showed significantly decreased endothelium-dependent relaxations induced by acetylcholine compared with the aortae incubated in control glucose. Treatment with indomethacin, a cyclooxygenase inhibitor, or SQ29548, a prostaglandin H2/thromboxane A2 receptor antagonist, restored acetylcholine relaxations of rings in elevated glucose to normal, while these agents had no effect on the relaxation of rings incubated in control glucose. Aortae incubated with mannose (44 mM) as a hyperosmotic control relaxed to acetylcholine normally. The relaxations in response to A23187 and sodium nitroprusside were not different between rings exposed to control and elevated glucose. Radioimmunoassay measurements showed a significant increase in acetylcholine-stimulated release of thromboxane A2 and prostaglandin F2.alpha. in aortae with, but not without endothelium incubated with elevated, but not with control glucose. Thus a possible mechanism for endothelium dysfunction in diabetes mellitus is the hyperglycemia-induced increased generation of endothelium-derived vasoconstrictor prostanoids.