Koller Akos, Bagi Zsolt
Dept. of Physiology, New York Medical College, Valhalla, NY 10595, USA.
Am J Physiol Heart Circ Physiol. 2004 Dec;287(6):H2461-7. doi: 10.1152/ajpheart.00295.2004. Epub 2004 Aug 19.
The role of metabolic factors derived from cardiac muscle in the development of reactive hyperemia after brief occlusions of the coronary circulation seems to be well established. However, the contribution of occlusion-induced changes in hemodynamic forces to eliciting reactive hyperemia is less known. We hypothesized that in isolated coronary arterioles changes in intraluminal pressure and flow, during and after release of occlusion (O/R), themselves via activating intrinsic mechanosensitive mechanisms, elicit release of vasoactive factors resulting in reactive dilations. Thus in isolated coronary arterioles (diameter: 88 +/- 8 microm) changes in diameter to changes in pressure or pressure plus flow (P+F) during and after a brief period (30, 60, and 120 s) of O/R of cannulating tube were measured by videomicroscopy. In response to both types of O/R, diameter first decreased, then, subsequently increased during occlusions. When only pressure was changed (from 80-10-80 mmHg), after release of occlusion, peak dilations increased as a function of the duration of occlusions. After flow was established (30 microl/min), O/R elicited changes in both pressure and flow (from 80-10-80 mmHg and from 0 to 30 microl/min). In these conditions, after the release of occlusions, not only the peak but also the duration of reactive dilation increased significantly as a function of the length of occlusions. The dilations during, and peak dilations after occlusions both in pressure and P+F protocols were significantly reduced by the inhibition of NO synthase with Nomega-nitro-L-arginine-methyl-ester (L-NAME) or by endothelium removal, whereas duration of postocclusion dilations were reduced by L-NAME or by endothelium removal only in P+F protocols. Furthermore, in both protocols, catalase significantly reduced the peak but not the duration of reactive dilations. Thus, mechanosensitive mechanisms that are sensitive to deformation, pressure, stretch, and wall shear stress elicit release of NO and H2O2, resulting in reactive dilation of isolated coronary arterioles.
心肌衍生的代谢因子在冠状动脉循环短暂闭塞后反应性充血发展中的作用似乎已得到充分证实。然而，闭塞诱导的血流动力学力变化对引发反应性充血的贡献却鲜为人知。我们推测，在离体冠状动脉小动脉中，闭塞（O/R）期间及之后管腔内压力和流量的变化，通过激活内在机械敏感机制，引发血管活性因子的释放，从而导致反应性扩张。因此，通过视频显微镜测量了在插管短暂（30、60和120秒）O/R期间及之后，离体冠状动脉小动脉（直径：88±8微米）直径对压力或压力加流量（P+F）变化的反应。针对两种类型的O/R，直径在闭塞期间先减小，随后增大。当仅改变压力（从80 - 10 - 80 mmHg）时，闭塞解除后，峰值扩张随闭塞持续时间的增加而增大。在建立流量（30微升/分钟）后，O/R引发压力和流量的变化（从80 - 10 - 80 mmHg和从0到30微升/分钟）。在这些条件下，闭塞解除后，不仅反应性扩张的峰值，而且其持续时间均随闭塞长度的增加而显著增加。在压力和P+F方案中，用Nω-硝基-L-精氨酸甲酯（L-NAME）抑制一氧化氮合酶或去除内皮，均可显著降低闭塞期间的扩张以及闭塞后峰值扩张，而仅在P+F方案中，L-NAME或去除内皮可减少闭塞后扩张的持续时间。此外，在两种方案中，过氧化氢酶均可显著降低反应性扩张的峰值，但不影响其持续时间。因此，对变形、压力、拉伸和壁面剪应力敏感的机械敏感机制引发一氧化氮和过氧化氢的释放，导致离体冠状动脉小动脉反应性扩张。
