Heat and α1-adrenergic responsiveness in human skeletal muscle feed arteries: the role of nitric oxide
Heat and α1-adrenergic responsiveness in human skeletal muscle feed arteries: the role of nitric oxide
复制标题
DOI：
10.1152/japplphysiol.00955.2012
复制
发表时间：
2012-12-01
影响因子：
3.3
通讯作者：
Richardson, Russell S.
中科院分区：
文献类型：
--
作者：
Ives, Stephen J.;Andtbacka, Robert H. I.;Richardson, Russell S.
伊韦斯SJ，Andtbacka RH，Kwon SH，Shiu YT，Ruan T，Noyes RD，Zhang QJ，Symons JD，Richardson RS.人骨骼肌供血动脉的热和α（1）肾上腺素能反应：一氧化氮的作用。J Appl Physiol 113：1690-1698，2012.首次发表于2012年10月4日; doi：10.1152/japplphysiol.00955.2012.-局部温度升高对人骨骼肌供血动脉产生交感神经阻滞作用。我们推测，这种减弱的α（1）-肾上腺素能受体反应性可能是由于温度诱导的一氧化氮（NO）生物利用度增加，从而减少了α 1-肾上腺素能受体激动剂苯肾上腺素（PE）的影响。收集13条人骨骼肌供血动脉，并使用钢丝肌造影术在37 ℃和39 ℃下产生PE浓度-反应曲线，有和没有NO合酶（NOS）抑制剂N-G-单甲基-L-精氨酸（L-NMMA）。将一组动脉（n = 4）暴露于37 ℃或39 ℃，并通过Western印迹分析测定内皮NOS（eNOS）和α（1）-肾上腺素能受体的蛋白含量。此外，将培养的牛内皮细胞暴露于37 ℃和39 ℃的静态或剪切应力条件下，并测定eNOS活化（Ser（1177）处的磷酸化）、eNOS表达和NO代谢物[硝酸盐+亚硝酸盐（NOx）]。39 ℃时PE诱导的最大血管收缩（PEmax）低于37 ℃时[39 +/- 10 vs. 84 +/- 30%对100 mM KCl的最大反应（KClmax）]。NO阻断使39 ℃时的血管收缩恢复到37 ℃时的水平（80 +/-26%KClmax）。对供血动脉的蛋白质印迹分析显示，加热增加了eNOS蛋白，但没有增加α（1）-肾上腺素能受体。加热牛内皮细胞导致更大的剪切应力诱导的eNOS激活和NOx的生产。总之，这些数据首次揭示，在人骨骼肌供血动脉中，NO阻断可以恢复热衰减的α（1）-肾上腺素能受体介导的血管收缩，并暗示内皮衍生的NO生物利用度是热诱导的交感神经溶解的主要贡献者。因此，这些发现强调了血管扩张剂在调节血管对血管收缩剂的反应中的重要作用。
Ives SJ, Andtbacka RH, Kwon SH, Shiu YT, Ruan T, Noyes RD, Zhang QJ, Symons JD, Richardson RS. Heat and alpha(1)-adrenergic responsiveness in human skeletal muscle feed arteries: the role of nitric oxide. J Appl Physiol 113: 1690-1698, 2012. First published October 4, 2012; doi: 10.1152/japplphysiol.00955.2012.-Increased local temperature exerts a sympatholytic effect on human skeletal muscle feed arteries. We hypothesized that this attenuated alpha(1)-adrenergic receptor responsiveness may be due to a temperature-induced increase in nitric oxide (NO) bioavailability, thereby reducing the impact of the alpha 1-adrenergic receptor agonist phenylephrine (PE). Thirteen human skeletal muscle feed arteries were harvested, and wire myography was used to generate PE concentration-response curves at 37 degrees C and 39 degrees C, with and without the NO synthase (NOS) inhibitor N-G-monomethyl-L-arginine (L-NMMA). A subset of arteries (n = 4) were exposed to 37 degrees C or 39 degrees C, and the protein content of endothelial NOS (eNOS) and alpha(1)-adrenergic receptors was determined by Western blot analysis. Additionally, cultured bovine endothelial cells were exposed to static or shear stress conditions at 37 degrees C and 39 degrees C and assayed for eNOS activation (phosphorylation at Ser(1177)), eNOS expression, and NO metabolites [nitrate + nitrite (NOx)]. Maximal PE-induced vasocontraction (PEmax) was lower at 39 degrees C than at 37 degrees C [39 +/- 10 vs. 84 +/- 30% maximal response to 100 mM KCl (KClmax)]. NO blockade restored vasocontraction at 39 degrees C to that achieved at 37 degrees C (80 +/- 26% KClmax). Western blot analysis of the feed arteries revealed that heating increased eNOS protein, but not alpha(1)-adrenergic receptors. Heating of bovine endothelial cells resulted in greater shear stress-induced eNOS activation and NOx production. Together, these data reveal for the first time that, in human skeletal muscle feed arteries, NO blockade can restore the heat-attenuated alpha(1)-adrenergic receptor-mediated vasocontraction and implicate endothelium-derived NO bioavailability as a major contributor to heat-induced sympatholysis. Consequently, these findings highlight the important role of vasodilators in modulating the vascular response to vasoconstrictors.