Cooke J P, Stamler J, Andon N, Davies P F, McKinley G, Loscalzo J
Division of Vascular Medicine and Atherosclerosis, Brigham and Women's Hospital, Boston 02115.
Am J Physiol. 1990 Sep;259(3 Pt 2):H804-12. doi: 10.1152/ajpheart.1990.259.3.H804.
We designed a novel system to study flow-mediated endothelium-dependent vasodilation. Vascular rings of rabbit thoracic aorta were mounted for isometric tension recording in a flow chamber filled with physiological saline solution. The flow chamber contained a stir bar and was mounted on a magnetic stirrer to induce vortical flow. Norepinephrine (NE, 10(-6) M) induced contraction of the vascular rings. Bovine endothelial cells on microcarrier beads added to the chamber had little effect on contraction to NE in the absence of flow. Flow induced endothelium-dependent relaxation of the vascular rings that was dependent on the flow rate. Relaxations were annulled or reversed to a contraction with methylene blue, bovine hemoglobin, or N-monomethyl-L-arginine. Conversely, N-acetyl-L-cysteine augmented the flow-mediated relaxation. Furthermore, in the presence of N-acetyl-L-cysteine, the half-life of the endothelium-dependent relaxing factor was increased. In conclusion, the stimulus of flow induces the release by endothelial cells of a diffusible, short-lived factor with the attributes of a nitrovasodilator. The action of this endogenous vasodilator is augmented by the reduced thiol N-acetyl-L-cysteine.
我们设计了一种新型系统来研究血流介导的内皮依赖性血管舒张。将兔胸主动脉血管环安装在充满生理盐溶液的流动腔室中，用于等长张力记录。流动腔室包含一个搅拌棒，并安装在磁力搅拌器上以诱导涡流。去甲肾上腺素（NE，10^(-6) M）诱导血管环收缩。在无血流的情况下，添加到腔室中的微载体珠上的牛内皮细胞对NE诱导的收缩影响很小。血流诱导血管环产生内皮依赖性舒张，且这种舒张依赖于流速。亚甲蓝、牛血红蛋白或N-单甲基-L-精氨酸可消除舒张或使其逆转至收缩。相反，N-乙酰-L-半胱氨酸增强了血流介导的舒张。此外，在N-乙酰-L-半胱氨酸存在的情况下，内皮依赖性舒张因子的半衰期延长。总之，血流刺激诱导内皮细胞释放一种具有硝基血管舒张剂特性的可扩散、寿命短暂的因子。这种内源性血管舒张剂的作用被还原型硫醇N-乙酰-L-半胱氨酸增强。
