Research Unit, Regional Hospital Randers, Randers, Denmark.
Department of Biomedicine, Aarhus University , Aarhus , Denmark.
Am J Physiol Heart Circ Physiol. 2019 Jan 1;316(1):H245-H254. doi: 10.1152/ajpheart.00368.2018. Epub 2018 Nov 16.
Inadequate perfusion of solid cancer tissue results in low local nutrient and oxygen levels and accumulation of acidic waste products. Previous investigations have focused primarily on tumor blood vessel architecture, and we lack information concerning functional differences between arteries that deliver blood to solid cancer tissue versus normal tissue. Here, we use isometric myography to study resistance-sized arteries from human primary colon adenocarcinomas and matched normal colon tissue. Vasocontraction of colon cancer feed arteries in response to endothelin-1 and thromboxane stimulation is attenuated compared with normal colon arteries despite similar wall dimensions and comparable contractions to arginine vasopressin and K-induced depolarization. Acetylcholine-induced vasorelaxation and endothelial NO synthase expression are increased in colon cancer feed arteries compared with normal colon arteries, whereas vasorelaxation to exogenous NO donors is unaffected. In congruence, the differences in vasorelaxant and vasocontractile function between colon cancer feed arteries and normal colon arteries decrease after NO synthase inhibition. Rhythmic oscillations in vascular tone, known as vasomotion, are of lower amplitude but similar frequency in colon cancer feed arteries compared with normal colon arteries. In conclusion, higher NO synthase expression and elevated NO signaling amplify vasorelaxation and attenuate vasocontraction of human colon cancer feed arteries. We propose that enhanced endothelial function augments tumor perfusion and represents a potential therapeutic target. NEW & NOTEWORTHY Local vascular resistance influences tumor perfusion. Arteries supplying human colonic adenocarcinomas show enhanced vasorelaxation and reduced vasocontraction mainly due to elevated nitric oxide-mediated signaling. Rhythmic oscillations in tone, known as vasomotion, are attenuated in colon cancer feed arteries.
实体瘤组织灌注不足会导致局部营养和氧气水平降低，并积累酸性废物。先前的研究主要集中在肿瘤血管结构上，我们缺乏有关向实体瘤组织输送血液的动脉与正常组织之间功能差异的信息。在这里，我们使用等长肌描记术研究来自人原发性结肠腺癌和匹配的正常结肠组织的阻力大小的动脉。尽管壁尺寸相似，并且对精氨酸加压素和 K 引起的去极化的收缩相似，但与正常结肠动脉相比，内皮素-1和血栓素刺激引起的结肠癌细胞滋养动脉的血管收缩减弱。与正常结肠动脉相比，乙酰胆碱诱导的血管舒张和内皮型一氧化氮合酶表达增加，但对外源性一氧化氮供体的血管舒张作用不受影响。一致地，在一氧化氮合酶抑制后，结肠癌细胞滋养动脉与正常结肠动脉之间的血管舒张和血管收缩功能的差异减小。称为血管舒缩的血管张力的节律性振荡在结肠癌细胞滋养动脉中的幅度较低，但频率与正常结肠动脉相似。总之，较高的一氧化氮合酶表达和升高的一氧化氮信号放大了人结肠癌细胞滋养动脉的血管舒张，并减弱了其血管收缩。我们提出增强的内皮功能增强了肿瘤灌注，并代表了一个潜在的治疗靶点。新的和值得注意的是，局部血管阻力会影响肿瘤灌注。供应人类结肠腺癌的动脉显示出增强的血管舒张和减少的血管收缩，主要是由于升高的一氧化氮介导的信号。称为血管舒缩的张力的节律性振荡在结肠癌滋养动脉中减弱。
