Cardiac endothelial cells modulate contractility of rat heart in response to oxygen tension and coronary flow.
Cardiac endothelial cells modulate contractility of rat heart in response to oxygen tension and coronary flow.
复制标题
心脏内皮细胞响应氧张力和冠状动脉流量调节大鼠心脏的收缩力。
DOI：
10.1161/01.res.72.5.1044
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发表时间：
1993
影响因子：
20.1
通讯作者：
Winegrad,S
中科院分区：
文献类型：
--
作者：
Ramaciotti,C;McClellan,G;Sharkey,A;Rose,D;Weisberg,A;Winegrad,S
这项研究的目的是确定心脏内皮细胞是否向冠脉灌注液中释放改变心肌细胞收缩能力的物质。为了测定流经冠状动脉血管的液体对心肌收缩性能的影响，基于级联原理发展了一种研究血管平滑肌功能的新方法。定期收集离体心冠状静脉流出液，复氧后作为另一心内膜分离小梁的洗浴介质。冠状静脉流出物改变了离体骨小梁的收缩。变化的幅度和方向取决于冠脉流出物复氧前的氧饱和度和收集冠脉流出物时的冠脉流量。在Krebs‘s溶液中暴露0.5%Triton X-100 1秒，可显著改变小梁对冠脉流出物的反应，破坏心内皮细胞。通过破坏产生流出物的灌流心脏和检测流出物的小梁中的内皮细胞，它被完全消除。因此，冠脉流出液中心脏活性物质的存在需要内皮细胞。已经证实，不稳定的内皮来源的上调(正性变力)因子和更稳定的内皮来源的下调(负性变力)因子的产生似乎解释了冠脉流出物引起的心肌收缩能力的所有变化。在分离的灌流心脏中显示的内皮衍生物质都不是一氧化氮或内皮素。内皮源性上调因子的浓度对氧分压敏感，而内皮下调因子的浓度对冠脉流量敏感，但对氧分压不敏感。冠脉流出物似乎含有刺激内皮细胞分泌的物质(内皮前因子)以及内皮细胞产生的物质(内皮因子)。结果表明，在灌流介质通过冠状动脉血管系统的过程中，上调和下调因子以相对浓度被添加到灌流液中，该浓度至少部分取决于局部组织的PO2和冠脉血流的速度。在完好无损的心脏中，这种机制可以维持能量供应和所做功之间的平衡。
The aim of this study was to determine if endothelial cells in the heart release substances into the coronary perfusion medium that modify the contractility of myocardial cells. To assay the effects on the contractility of cardiac muscle of fluid that has passed through the coronary vasculature, a new method has been developed based on the cascade principle used to study vascular smooth muscle function. The coronary venous effluent from an isolated perfused working heart was collected periodically, and after reoxygenation it was used as the bathing medium for trabeculae isolated from the endocardial surface of another heart. The coronary venous effluent changed the contraction of the isolated trabeculae. The amplitude and the direction of the change depended on the degree of oxygen saturation of the coronary effluent before it was reoxygenated and the rate of coronary flow at the time the effluent was collected. The response of the trabecula to the coronary effluent was substantially altered by damaging the endocardial endothelium with a 1-second exposure to 0.5% Triton X-100 in Krebs' solution. It was completely eliminated by damaging endothelial cells in both the perfused heart producing the effluent and the trabecula on which the effluent was assayed. Therefore, endothelial cells are required for the presence of cardioactive substances in the coronary effluent. The production of a labile endothelium-derived upregulating (positively inotropic) factor and a more stable endothelium-derived downregulating (negatively inotropic) factor has been demonstrated and appears to account for all of the changes in myocardial contractility produced by the coronary effluent. Neither of the endothelium-derived substances demonstrated in the isolated perfused heart is nitric oxide or endothelin. The concentration of the endothelium-derived upregulating factor is sensitive to oxygen tension, whereas the concentration of the endothelium-derived downregulating factor is sensitive to the rate of coronary flow but not oxygen tension. The coronary effluent appears to contain substances that stimulate secretion by the endothelial cells (preendothelial factors) as well as substances that have been produced by the endothelial cells (endothelial factors). The results indicate that during the passage of perfusion medium through the coronary vasculature upregulating and downregulating factors are added to the perfusate in relative concentrations that depend at least in part on local tissue PO2 and the rate of coronary flow. In the intact heart, this mechanism could operate to maintain balance between energy supply and work performed.