Korac A, Buzadzic B, Petrovic V, Vasilijevic A, Jankovic A, Micunovic K, Korac B
Institute of Zoology, Faculty of Biology, University of Belgrade, Belgrade, Serbia.
Histol Histopathol. 2008 Apr;23(4):441-50. doi: 10.14670/HH-23.441.
Cold exposure has been shown to increase blood flow in interscapular brown adipose tissue (IBAT). The aim of the present study was to evaluate the role of the L-arginine-nitric oxide (NO) pathway on IBAT capillary network remodeling and its possible correlation with superoxide anion radical (O2(-)). In the rats that received L-arginine (2.25%) or NG-nitro-L-arginine methyl ester (L-NAME, 0.01%) as a drinking liquid and maintained at room (22+/-1 degrees C) or low (4+/-1 degrees C) temperature for 45 days, IBAT capillaries were analyzed by stereology and observed by light and electron microscopy. Additionally, endothelial *NO synthase (eNOS) expression, nitrotyrosine immunoreactivity and both copper zinc superoxide dismutase (CuZnSOD) enzyme activity and immunohistochemical localization were examined. Stereological analyses of IBAT show that the capillary volume density, as well as capillary-to-brown adipocytes ratio, are increased in cold. L-arginine treatment increases, while L-NAME decreases both parameters, compared to respective controls. Those changes were accompanied by capillary dilatation observed by light and electron microscopy. The activity of CuZnSOD is lower in control cold-acclimated rats, as well as in both L-arginine-treated groups, when compared to control animals acclimated to room temperature. L-NAME treatment attenuates the effects both of cold and L-arginine on CuZnSOD and increases immunopositivity for CuZnSOD in room temperature-acclimated rats. Our results show that NO induces remodeling of the IBAT capillary network by angiogenesis, and presumably that interaction with O2(-) has a role in that modulation. The increased eNOS expression accompanied by an increased nitrotyrosine immunoreaction observed in both L-arginine-treated groups compared to corresponding controls strengthens this hypothesis.
研究表明，冷暴露可增加肩胛间棕色脂肪组织（IBAT）的血流量。本研究的目的是评估L-精氨酸-一氧化氮（NO）途径在IBAT毛细血管网络重塑中的作用及其与超氧阴离子自由基（O2(-)）的可能相关性。将接受L-精氨酸（2.25%）或NG-硝基-L-精氨酸甲酯（L-NAME，0.01%）作为饮用水的大鼠，分别置于室温（22±1℃）或低温（4±1℃）环境中45天，采用体视学方法分析IBAT毛细血管，并通过光镜和电镜进行观察。此外，检测内皮型*NO合酶（eNOS）表达、硝基酪氨酸免疫反应性以及铜锌超氧化物歧化酶（CuZnSOD）的酶活性和免疫组化定位。对IBAT的体视学分析表明，寒冷条件下毛细血管体积密度以及毛细血管与棕色脂肪细胞的比例均增加。与各自的对照组相比，L-精氨酸处理可增加这两个参数，而L-NAME处理则使其降低。这些变化伴随着光镜和电镜下观察到的毛细血管扩张。与适应室温的对照动物相比，对照冷适应大鼠以及两个L-精氨酸处理组中CuZnSOD的活性均较低。L-NAME处理减弱了寒冷和L-精氨酸对CuZnSOD的影响，并增加了室温适应大鼠中CuZnSOD的免疫阳性率。我们的结果表明，NO通过血管生成诱导IBAT毛细血管网络重塑，推测与O2(-)的相互作用在这种调节中起作用。与相应对照组相比，两个L-精氨酸处理组中观察到的eNOS表达增加以及硝基酪氨酸免疫反应增强支持了这一假设。
