Sun D, Huang A, Sharma S, Koller A, Kaley G
Department of Physiology, New York Medical College, Valhalla, New York 10595, USA.
Am J Physiol Heart Circ Physiol. 2001 May;280(5):H2087-93. doi: 10.1152/ajpheart.2001.280.5.H2087.
The cytoskeleton is believed to have an important role in the structural and functional integrity of endothelial cells. The role of the endothelial cytoskeleton, specifically microtubules, in the mediation of flow-induced dilation of arterioles has not yet been studied. Thus the aim of our study was to investigate the role of microtubules in the endothelial mechanotransduction of flow-induced dilation of isolated gracilis arterioles of the rat. The active diameter of arterioles at a constant perfusion pressure (80 mmHg) was approximately 63 microm, whereas their passive diameter (Ca(2+)-free solution) was approximately 119 microm. At a constant pressure, increases in flow of the perfusate solution (from 0 to 10 and from 10 to 20 microl/min) elicited increases in diameter up to approximately 95 microm (approximately a 53% increase). Intraluminal administration of nocodazole at concentrations of 5 x 10(-9) and 5 x 10(-8) M had no discernible effects on the structure of endothelial microtubules or on flow-induced dilation, whereas it disassembled microtubules and eliminated flow-induced dilation at a concentration of 5 x 10(-7) M. At this higher concentration, however, the basal diameter and dilations to acetylcholine (10(-8) M), sodium nitroprusside (10(-7) M), arachidonic acid (5 x 10(-6) M), and prostaglandin E2 (10(-8) M) were unaffected. Colchicine (5 x 10(-7) M) also disassembled microtubules and eliminated flow-induced dilation. We concluded that, in isolated arterioles, the integrity of the endothelial cytoskeleton is essential for the transduction of the shear stress signal that results in the release of endothelial factors evoking dilation.
细胞骨架被认为在内皮细胞的结构和功能完整性中发挥重要作用。内皮细胞骨架，特别是微管，在介导小动脉血流诱导的扩张中的作用尚未得到研究。因此，我们研究的目的是探讨微管在大鼠离体股薄肌小动脉血流诱导扩张的内皮机械转导中的作用。在恒定灌注压力（80 mmHg）下，小动脉的活性直径约为63微米，而其被动直径（无钙溶液）约为119微米。在恒定压力下，灌注液流量增加（从0到10以及从10到20微升/分钟）会使直径增加至约95微米（约增加53%）。腔内给予浓度为5×10⁻⁹和5×10⁻⁸ M的诺考达唑对内皮微管结构或血流诱导的扩张没有明显影响，而在浓度为5×10⁻⁷ M时它会拆散微管并消除血流诱导的扩张。然而，在这个较高浓度下，基础直径以及对乙酰胆碱（10⁻⁸ M）、硝普钠（10⁻⁷ M）、花生四烯酸（5×10⁻⁶ M）和前列腺素E2（10⁻⁸ M）的扩张不受影响。秋水仙碱（5×10⁻⁷ M）也会拆散微管并消除血流诱导的扩张。我们得出结论，在离体小动脉中，内皮细胞骨架的完整性对于剪切应力信号的转导至关重要，该信号导致释放引起扩张的内皮因子。
