Gilbert Raymond D, Pearce William J, Longo Lawrence D
Departments of Physiology and Pharmacology, Center for Perinatal Biology, School of Medicine, Loma Linda University, Loma Linda, CA, USA.
High Alt Med Biol. 2003 Summer;4(2):203-13. doi: 10.1089/152702903322022802.
In response to high altitude long-term hypoxemia, the heart of fetal sheep shows a decrease in cardiac output that is secondary to a decrease in myocardial cell contractile function. The intracellular mechanisms responsible for these reductions might include reduced myofibrillar Mg(2+)-activated ATPase. There is also a decrease in beta(1)-adrenergic receptor stimulated augmentation of myocardial contraction. An overproduction of cAMP by beta(1)-adrenergic receptor stimulation, resulting in overphosphorylation of troponin I, may reduce calcium binding by troponin C. Fetal coronary arteries have a reduced contractile response to K(+) depolarization and a reduced sensitivity to a thromboxane A(2) receptor agonist-stimulated contraction. Cerebral arteries of adult sheep (but not the fetus) show decreased responses to both K(+)-depolarization and norepinephrine-induced contraction. Nonetheless, cerebral arteries in the long-term hypoxic fetus demonstrated a number of significant changes from control. For the cerebral arteries in general, high altitude hypoxia is associated with augmented or upregulation of presynaptic functions. In contrast, postsynaptic functions tend to be significantly depressed or downregulated. The results emphasize the role of high altitude, long-term hypoxemia in modulating adrenergic- and serotonergic-mediated signal transduction in the cerebral vasculature. They specifically highlight the significant differences in acclimatization responses between the fetus and adult.
为应对高原长期低氧血症，胎羊心脏的心输出量减少，这是心肌细胞收缩功能下降的继发结果。导致这些降低的细胞内机制可能包括肌原纤维镁激活ATP酶减少。β1肾上腺素能受体刺激引起的心肌收缩增强也有所降低。β1肾上腺素能受体刺激导致cAMP过度产生，进而使肌钙蛋白I过度磷酸化，这可能会减少肌钙蛋白C与钙的结合。胎儿冠状动脉对钾去极化的收缩反应降低，对血栓素A2受体激动剂刺激的收缩敏感性降低。成年绵羊（而非胎儿）的脑动脉对钾去极化和去甲肾上腺素诱导的收缩反应均降低。尽管如此，长期缺氧胎儿的脑动脉与对照组相比仍表现出一些显著变化。一般而言，对于脑动脉，高原缺氧与突触前功能增强或上调有关。相反，突触后功能往往会显著抑制或下调。这些结果强调了高原长期低氧血症在调节脑血管中肾上腺素能和5-羟色胺能介导的信号转导中的作用。它们特别突出了胎儿和成年个体在适应反应方面的显著差异。
