Reduced Heart Rate and Cardiac Output Differentially Affect Angiogenesis, Growth, and Development in Early Chicken Embryos (Gallus domesticus)
Reduced Heart Rate and Cardiac Output Differentially Affect Angiogenesis, Growth, and Development in Early Chicken Embryos (Gallus domesticus)
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DOI：
10.1086/670594
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发表时间：
2013-05-01
影响因子：
1.6
通讯作者：
Burggren, Warren
中科院分区：
文献类型：
--
作者：
Branum, Sylvia R.;Yamada-Fisher, Miho;Burggren, Warren
鸡胚发育中的血管系统中血管周向张力和切应力的增加已被假设为刺激发育中的外周循环绒毛尿囊膜（CAM）中的血管生成。为了验证这一假设，在急性和慢性局部应用纯心动过缓药物ZD 7288后，在早期鸡胚中测量CAM中的血管生成、发育和生长。在第56小时，ZD 7288使心率（f（H））降低约30%，但对每搏输出量（约0.19 +/- 0.2 μ L）无显著影响，导致心输出量（CO）从约27 +/- 3降至18 +/- 2 μ L min（-1）。发育72小时时的平均f（H）通过急性ZD 7288处理（250 μ M）同样显着降低至128 +/- 0.3次/分钟（-1），而对照组和Pannett-Compton（P-C）盐水处理的胚胎分别为174.5 +/- 0.3和174.7 +/- 0.8次/分钟（-1）。ZD 7288长期给药以及伴随的f（H）和CO降低在120 h时未改变眼直径或颈椎屈曲（发育率的关键指标），但显著降低了总体生长（湿体重和干体重降低20%）。CAM血管密度指数（反映血管生成）测量200-400 μ m从脐茎没有改变，但ZD 7288减少血管数量，因此血管密度13%-16%更远（500-600 μ m从脐茎）在CAM。在ZD 7288处理的胚胎中，在第二个分支顺序内发现血管长度减少（类似于距脐带300-400 μ m），而在更靠近脐带处发现血管直径减少，从第一个分支顺序开始（类似于200-300 μ m）。奇怪的是，长期应用P-C生理盐水也使500和600 mm处的外周CAM血管密度指数分别降低了13%和7%，这可能是由于局部血管生成因子的洗脱。总之，降低f（H）和降低CO并不会减慢发育速率，但会降低胚胎生长速率和CAM周围的血管生成。这项研究首次证明了早期脊椎动物胚胎个体发育中的不同过程（即，肥大生长与发育）对改变对流血流具有不同的敏感性。
An increase in both vascular circumferential tension and shear stress in the developing vasculature of the chicken embryo has been hypothesized to stimulate angiogenesis in the developing peripheral circulation chorioallantoic membrane (CAM). To test this hypothesis, angiogenesis in the CAM, development, and growth were measured in the early chicken embryo, following acute and chronic topical application of the purely bradycardic drug ZD7288. At hour 56, ZD7288 reduced heart rate (f(H)) by similar to 30% but had no significant effect on stroke volume (similar to 0.19 +/- 0.2 mu L), collectively resulting in a significant fall in cardiac output (CO) from similar to 27 +/- 3 to 18 +/- 2 mu L min(-1). Mean f(H) at 72 h of development was similarly significantly lowered by acute ZD7288 treatment (250 mu M) to 128 +/- 0.3 beats min(-1), compared with 174.5 +/- 0.3 and 174.7 +/- 0.8 beats min(-1) in control and Pannett-Compton (P-C) saline-treated embryos, respectively. Chronic dosing with ZD7288-and the attendant decreases in f(H) and CO-did not change eye diameter or cervical flexion (key indicators of development rate) at 120 h but significantly reduced overall growth (wet and dry body mass decreased by 20%). CAM vessel density index (reflecting angiogenesis) measured 200-400 mu m from the umbilical stalk was not altered, but ZD7288 reduced vessel numbers-and therefore vessel density-by 13%-16% more distally (500-600 mu m from umbilical stalk) in the CAM. In the ZD7288-treated embryos, a decrease in vessel length was found within the second branch order (similar to 300-400 mu m from the umbilical stock), while a decrease in vessel diameter was found closer to the umbilical stock, beginning in the first branch order (similar to 200-300 mu m). Paradoxically, chronic application of P-C saline also reduced peripheral CAM vessel density index at 500 and 600 mm by 13% and 7%, respectively, likely from washout of local angiogenic factors. In summary, decreased f(H) with reduced CO did not slow development rate but reduced embryonic growth rate and angiogenesis in the CAM periphery. This study demonstrates for the first time that different processes in the ontogeny of the early vertebrate embryo (i.e., hypertrophic growth vs. development) have differential sensitivities to altered convective blood flow.