Department of Physical Education, Institute of Bioscience, University of São Paulo State-UNESP, Rio Claro, São Paulo, Brazil.
PLoS One. 2012;7(12):e53318. doi: 10.1371/journal.pone.0053318. Epub 2012 Dec 28.
The majority of studies have investigated the effect of exercise training (TR) on vascular responses in diabetic animals (DB), but none evaluated nitric oxide (NO) and advanced glycation end products (AGEs) formation associated with oxidant and antioxidant activities in femoral and coronary arteries from trained diabetic rats. Our hypothesis was that 8-week TR would alter AGEs levels in type 1 diabetic rats ameliorating vascular responsiveness.
METHODOLOGY/PRINCIPAL FINDINGS: Male Wistar rats were divided into control sedentary (C/SD), sedentary diabetic (SD/DB), and trained diabetic (TR/DB). DB was induced by streptozotocin (i.p.: 60 mg/kg). TR was performed for 60 min per day, 5 days/week, during 8 weeks. Concentration-response curves to acetylcholine (ACh), sodium nitroprusside (SNP), phenylephrine (PHE) and tromboxane analog (U46619) were obtained. The protein expressions of eNOS, receptor for AGEs (RAGE), Cu/Zn-SOD and Mn-SOD were analyzed. Tissues NO production and reactive oxygen species (ROS) generation were evaluated. Plasma nitrate/nitrite (NO(x)⁻), superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS) and N(ε)-(carboxymethyl) lysine (CML, AGE biomarker). A rightward shift in the concentration-response curves to ACh was observed in femoral and coronary arteries from SD/DB that was accompanied by an increase in TBARS and CML levels. Decreased in the eNOS expression, tissues NO production and NO(x)⁻ levels were associated with increased ROS generation. A positive interaction between the beneficial effect of TR on the relaxing responses to ACh and the reduction in TBARS and CML levels were observed without changing in antioxidant activities. The eNOS protein expression, tissues NO production and ROS generation were fully re-established in TR/DB, but plasma NO(x)⁻ levels were partially restored.
Shear stress induced by TR fully restores the eNOS/NO pathway in both preparations from non-treated diabetic rats, however, a massive production of AGEs still affecting relaxing responses possibly involving other endothelium-dependent vasodilator agents, mainly in coronary artery.
大多数研究都调查了运动训练（TR）对糖尿病动物（DB）血管反应的影响，但没有研究评估与氧化应激和抗氧化活性相关的一氧化氮（NO）和晚期糖基化终产物（AGEs）在训练糖尿病大鼠的股动脉和冠状动脉中的形成。我们的假设是，8 周的 TR 会改变 1 型糖尿病大鼠的 AGEs 水平，从而改善血管反应性。
方法/主要发现：雄性 Wistar 大鼠分为对照组安静（C/SD）、安静型糖尿病（SD/DB）和训练型糖尿病（TR/DB）。DB 通过链脲佐菌素（ip：60mg/kg）诱导。TR 每天进行 60 分钟，每周 5 天，持续 8 周。获得乙酰胆碱（ACh）、硝普钠（SNP）、苯肾上腺素（PHE）和血栓烷类似物（U46619）的浓度-反应曲线。分析内皮型一氧化氮合酶（eNOS）、AGEs 受体（RAGE）、Cu/Zn-SOD 和 Mn-SOD 的蛋白表达。评估组织 NO 产生和活性氧（ROS）生成。检测血浆硝酸盐/亚硝酸盐（NOx-）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、硫代巴比妥酸反应物质（TBARS）和 N（ε）-（羧甲基）赖氨酸（CML，AGE 生物标志物）。在 SD/DB 的股动脉和冠状动脉中，ACh 浓度-反应曲线出现右移，同时 TBARS 和 CML 水平升高。eNOS 表达减少，组织 NO 产生和 NOx-水平降低，与 ROS 生成增加有关。TR 对 ACh 松弛反应的有益作用与 TBARS 和 CML 水平降低之间存在正相互作用，而抗氧化活性没有改变。TR/DB 中 eNOS 蛋白表达、组织 NO 产生和 ROS 生成完全恢复，但血浆 NOx-水平部分恢复。
TR 产生的切应力完全恢复了未经治疗的糖尿病大鼠两种血管的 eNOS/NO 通路，但大量 AGEs 的产生仍会影响松弛反应，可能涉及其他内皮依赖性血管扩张剂，主要在冠状动脉。
