TOPICAL HYPERGLYCEMIA RAPIDLY SUPPRESSES EDRF-MEDIATED VASODILATION OF NORMAL RAT ARTERIOLES
TOPICAL HYPERGLYCEMIA RAPIDLY SUPPRESSES EDRF-MEDIATED VASODILATION OF NORMAL RAT ARTERIOLES
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DOI：
10.1152/ajpheart.1993.265.1.h219
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发表时间：
1993-07-01
影响因子：
--
通讯作者：
LASH, JM
中科院分区：
文献类型：
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作者：
BOHLEN, HG;LASH, JM
糖尿病早期，小动脉对内皮源性舒张因子（EDRF）的扩张受到抑制。本研究的目的是确定急性暴露于高血糖介质是否会抑制正常小动脉的 EDRF 功能。在血糖正常的大鼠局部暴露于含有浓度为 200、300 和 500 mg/100 ml D-葡萄糖的等渗溶液 1 小时之前和之后，测量了用离子电渗疗法应用乙酰胆碱 (ACh) 和硝普钠时肠小动脉的扩张情况。暴露于 200 mg/100 ml 浓度的 D-葡萄糖对乙酰胆碱的血管舒张没有影响。 300 mg/100 ml 和 500 mg/100 ml 的 D-葡萄糖浓度都会导致反应显着抑制：例如，在大约 50% 有效剂量 (100 nA) 下，D-葡萄糖浓度为 300 mg/100 ml 时，扩张反应降低 60%，而 D-葡萄糖浓度为 500 mg/100 ml 时，扩张反应降低 55%。暴露于 200、300 或 500 mg/100 ml 浓度的 D-葡萄糖后，硝普钠的反应并未显着受损 (P < 0.05)。暴露于 500 mg/100 ml 等渗 L-葡萄糖浓度 1 小时对 ACh 反应没有显着 (P > 0.05) 影响。在几乎所有测试的 ACh 剂量下，暴露于 500 mg/100 ml 的 D-葡萄糖浓度期间，用超氧化物歧化酶、过氧化氢酶、吲哚美辛或甲氯芬那酸进行预处理可保留 EDRF 介导的血管舒张作用。这些结果表明，在暴露于 D-葡萄糖高血糖期间，类二十烷酸合成增加而形成的氧自由基在其作用于微血管平滑肌之前会干扰 EDRF 机制。
Arteriolar dilation to endothelium-derived relaxing factor (EDRF) is suppressed early in diabetes mellitus. The purpose of this study was to determine whether acute exposure to a hyperglycemic media can suppress EDRF function of normal arterioles. Dilation of intestinal arterioles to iontophoretically applied acetylcholine (ACh) and nitroprusside was measured in normoglycemic rats before and after 1 h of topical exposure to isotonic solutions containing D-glucose concentrations of 200, 300, and 500 mg/100 ml. Exposure to a D-glucose concentration of 200 mg/100 ml had no effect on vasodilation to ACh. D-Glucose concentrations of both 300 and 500 mg/100 ml caused significant suppression of the responses: for example, at the approximate 50% effective dosage (100 nA), the dilatory response was decreased by 60% at a D-glucose concentration of 300 mg/100 ml and 55% at a D-glucose concentration of 500 mg/100 ml. Responses to nitroprusside were not significantly (P < 0.05) impaired after exposure to D-glucose concentrations of 200, 300, or 500 mg/100 ml. Exposure to an isotonic L-glucose concentration of 500 mg/100 ml for 1 h had no significant (P > 0.05) effect on responses to ACh. Pretreatment with superoxide dismutase, catalase, indomethacin, or meclofenamic acid preserved EDRF-mediated vasodilation during exposure to a D-glucose concentration of 500 mg/100 ml at almost all the ACh dosages tested. These results indicate that oxygen radicals formed in part by increased eicosanoid synthesis during exposure to D-glucose hyperglycemia interfere with the EDRF mechanism before its action on the microvascular smooth muscle.