Du X J, Dart A M
Baker Medical Research Institute, Prahran, Victoria, Australia.
Cardiovasc Res. 1993 Nov;27(11):2011-5. doi: 10.1093/cvr/27.11.2011.
The aim was to examine the time course of exocytotic and "spontaneous" noradrenaline overflow and the influence of an Uptake1 inhibitor, desipramine, in rat hearts subjected to anoxic and substrate-free perfusion.
Hearts were perfused with a constant flow and exocytotic noradrenaline overflow was elicited either by electrical stimulation of the left stellate ganglion or by K+ depolarisation. Noradrenaline overflow was measured by HPLC.
Energy depletion for a period of 30 min resulted in an enhanced spontaneous noradrenaline overflow and a progressive decline in the nerve stimulation induced noradrenaline overflow. However, noradrenaline overflow induced by 40 mM K+ was enhanced by three- to fourfold in the energy depleted conditions. During anoxia, desipramine (0.3 microM) inhibited the spontaneous noradrenaline overflow and partly increased, in the early phase of anoxia, noradrenaline overflow by nerve stimulation, but showed no effect on K+ induced overflow. Further experiments showed that K+ at 10 mM failed to evoke noradrenaline overflow in normoxic hearts but induced a significant overflow in energy depleted hearts, either in the presence or absence of desipramine; quantities of noradrenaline overflow in response to 10-40 mM K+ were substantially higher in anoxia. This difference in noradrenaline overflow caused by K+ during normoxia and anoxia was partly narrowed by desipramine which enhanced overflow in normoxia.
"Spontaneous" and exocytotic noradrenaline release coexist within the 30 min period of anoxia but their responses to Uptake1 inhibitor differ. K(+)-induced noradrenaline overflow was markedly augmented by energy depletion due to a combination of failed neuronal reuptake and enhanced exocytosis.
研究在无底物和缺氧灌注的大鼠心脏中，去甲肾上腺素胞吐和“自发性”溢出的时间进程，以及摄取1抑制剂地昔帕明的影响。
以恒定流量灌注心脏，通过电刺激左侧星状神经节或K⁺去极化引发去甲肾上腺素胞吐溢出。采用高效液相色谱法测量去甲肾上腺素溢出量。
30分钟的能量耗竭导致自发性去甲肾上腺素溢出增加，神经刺激诱导的去甲肾上腺素溢出逐渐下降。然而，在能量耗竭条件下，40 mM K⁺诱导的去甲肾上腺素溢出增加了三到四倍。在缺氧期间，地昔帕明（0.3 microM）抑制自发性去甲肾上腺素溢出，并在缺氧早期部分增加神经刺激引起的去甲肾上腺素溢出，但对K⁺诱导的溢出无影响。进一步实验表明，10 mM K⁺在正常氧合心脏中未能引发去甲肾上腺素溢出，但在能量耗竭的心脏中，无论有无地昔帕明，均诱导显著的溢出；在缺氧条件下，对10 - 40 mM K⁺反应的去甲肾上腺素溢出量显著更高。地昔帕明增加了正常氧合时的溢出，部分缩小了正常氧合和缺氧时K⁺引起的去甲肾上腺素溢出差异。
在缺氧的30分钟内存在“自发性”和胞吐性去甲肾上腺素释放，但它们对摄取1抑制剂的反应不同。由于神经元再摄取失败和胞吐作用增强，能量耗竭显著增加了K⁺诱导的去甲肾上腺素溢出。
