Cerebrovascular responsiveness to NG‐nitro‐L‐arginine methyl ester in spontaneously diabetic rats
Cerebrovascular responsiveness to NG‐nitro‐L‐arginine methyl ester in spontaneously diabetic rats
复制标题
自发性糖尿病大鼠脑血管对 NG-硝基-L-精氨酸甲酯的反应
DOI：
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发表时间：
1996
影响因子：
7.3
通讯作者：
I. Whittle
中科院分区：
文献类型：
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作者：
I. Fouyas;P. Kelly;I. Ritchie;I. Whittle
1 有证据表明内皮功能障碍与糖尿病有关。本研究的目的是评估自发性糖尿病胰岛素依赖性 BioBred (BB) 大鼠的局部脑血流量 (LCBF) 和脑血管对 NOS 抑制剂 NG-硝基-L-精氨酸甲酯 (L-NAME) 的反应性。 2 在通过完全定量 [14C]-碘安替比林放射自显影技术测量 LCBF 前 20 分钟，用 L-NAME（30 mg kg−1，静脉注射）或生理盐水治疗糖尿病大鼠和非糖尿病对照。 3 各组大鼠的生理参数（血液 pH、pH、PCO2 和 PO2、直肠温度、动脉血压或血浆葡萄糖）均无显着差异，糖尿病大鼠和非糖尿病大鼠对 L-NAME 的高血压反应的程度或时间特征也无差异。 4 在糖尿病大鼠中，观察到基础 LCBF 整体降低，尽管在测量的 13 个脑区中只有 5 个（主要是皮质下）发现显着降低（-20 至 -30% 之间）。注射 L-NAME 后，发现非糖尿病动物的 LCBF 显着降低（-20% 至 -40%）。在接受 L-NAME 治疗的糖尿病动物中，仅在下丘脑中测量到 LCBF 显着降低（-33%）。 5 在自发性糖尿病胰岛素依赖型 BB 大鼠中，急性 L-NAME 的脑血管反应减弱。这与已知与糖尿病相关的脑血管内皮功能障碍一致，并且除其他因素外，NO 诱导的扩张器张力的丧失可能是观察到的这些动物基础 LCBF 减少的基础。
1 There is evidence that endothelial dysfunction is associated with diabetes mellitus. The purpose of the present study was to assess local cerebral blood flow (LCBF) and cerebrovascular responsiveness to the NOS inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME) in spontaneously diabetic insulin‐dependent BioBred (BB) rats. 2 Diabetic rats, and non‐diabetic controls, were treated with L‐NAME (30 mg kg−1, i.v.) or saline, 20 min prior to the measurement of LCBF by the fully quantitative [14C]‐iodoantipyrine autoradiographic technique. 3 There were no significant differences in physiological parameters (blood pH, pH, PCO2, and PO2, rectal temperature, arterial blood pressure, or plasma glucose) between any of the groups of rats, and no difference in either the extent or the temporal characteristics of the hypertensive response to L‐NAME between diabetic and non‐diabetic rats. 4 In diabetic rats, a global reduction in basal LCBF was observed, although significant reductions (between −20 and −30%) were found in only 5 (mainly subcortical) out of the 13 brain regions measured. Following L‐NAME injection, significant reductions in LCBF (between −20 and −40%) were found in the non‐diabetic animals. In diabetic animals treated with L‐NAME, a significant reduction in LCBF was measured only in the hypothalamus (−33%). 5 The cerebrovascular response to acute L‐NAME is attenuated in spontaneously diabetic insulin‐dependent BB rats. This would be consistent with the endothelial dysfunction in cerebral vessels, known to be associated with diabetes mellitus and it is possible that a loss of NO‐induced dilator tone, amongst other factors, may underlie the observed reductions of basal LCBF in these animals.