Gavin T P, Wagner P D
Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Acta Physiol Scand. 2002 Jul;175(3):201-9. doi: 10.1046/j.1365-201X.2002.00987.x.
We investigated the vascular endothelial growth factor (VEGF) receptor [fms-like-tyrosine kinase (Flt-1 and fetal liver kinase-1 (Flk-1)] response to acute exercise. In female Wistar rats, the VEGF receptor messenger RNA (mRNA) response to a single acute exercise bout was examined using semi-quantitative Northern blot from the left gastrocnemius muscles at rest and post-exercise at 0, 1, 2, 4, 8, 16, 24 and 48 h. Exercise altered both Flt-1 and Flk-1 mRNA, with significant increases in Flt-1 mRNA at 1 and 24 h. However, post-hoc analysis was unable to discern the time point where a significant increase in Flk-1 mRNA occurred. To investigate the regulation of Flt-1 mRNA by exercise we examined if nitric oxide synthase (NOS) inhibition alters the Flt-1 mRNA response. Eight groups [
Rest or Exercise; Drug: Saline, 30 mg kg(-1)N(omega)-nitro-L-arginine methyl ester (L-NAME), 300 mg kg(-1) L-NAME or 300 mg kg(-1) D-NAME] were used to determine the effect of NOS inhibition on the Flt-1 mRNA response to exercise. L-NAME, a known NOS inhibitor, attenuated the exercise-induced increase in Flt-1 mRNA by approximately 50%. These findings suggest that: (1) exercise alters Flt-1 and Flk-1 gene expression; and (2) NO is important in the regulation of the Flt-1 gene response to exercise.
我们研究了血管内皮生长因子(VEGF)受体[类fms酪氨酸激酶(Flt-1)和胎儿肝激酶-1(Flk-1)]对急性运动的反应。在雌性Wistar大鼠中,使用半定量Northern印迹法检测了左腓肠肌在静息状态以及运动后0、1、2、4、8、16、24和48小时时,VEGF受体信使核糖核酸(mRNA)对单次急性运动的反应。运动改变了Flt-1和Flk-1的mRNA水平,Flt-1 mRNA在运动后1小时和24小时显著增加。然而,事后分析无法确定Flk-1 mRNA显著增加的时间点。为了研究运动对Flt-1 mRNA的调节作用,我们检测了一氧化氮合酶(NOS)抑制是否会改变Flt-1 mRNA的反应。使用八组实验[条件:静息或运动;药物:生理盐水、30 mg kg⁻¹ N⁻硝基-L-精氨酸甲酯(L-NAME)、300 mg kg⁻¹ L-NAME或300 mg kg⁻¹ D-NAME]来确定NOS抑制对运动诱导的Flt-1 mRNA反应的影响。已知的NOS抑制剂L-NAME使运动诱导的Flt-1 mRNA增加减弱了约50%。这些发现表明:(1)运动改变Flt-1和Flk-1基因表达;(2)一氧化氮在调节Flt-1基因对运动的反应中起重要作用。