Tatsumi K, Pickett C K, Weil J V
Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver 80262, USA.
Respir Physiol. 1995 Jul;101(1):47-57. doi: 10.1016/0034-5687(95)00012-3.
Previously we showed that prolonged exposure to severe hypoxia produces decreased peripheral chemoreceptor responsiveness to hypoxia and attenuates central nervous system (CNS) chemosensory translation, which together may contribute to the decreased hypoxic ventilatory response (HVR) in chronic hypoxia. In this study, we sought to determine whether the central or peripheral activity of endogenous dopamine modulates this decreased HVR. We examined the effects of peripheral and central dopamine receptor blockade on HVR and carotid sinus nerve (CNS) response to hypoxia in controls and in cats exposed to a simulated altitude of 5500 m for 3 weeks. Domperidone increased CSN response to hypoxia in hypoxic cats to levels similar to those observed in controls. HVR was also augmented by domperidone in hypoxic cats, but remained below that of controls. As a result, the CNS chemosensory translation remained reduced in hypoxic animals. We further treated animals with haloperidol. However, this combined treatment with domperidone and haloperidol led to no further increase in CSN or ventilatory responses to hypoxia, or in CNS chemosensory translation in hypoxic cats. Thus, decreased HVR in hypoxic cats is mediated both by depression of hypoxic sensitivity of the carotid body, which is largely dopaminergic, and by decreased CNS chemosensory translation which must involve non-dopaminergic mechanisms.
先前我们发现，长时间暴露于严重低氧环境会导致外周化学感受器对低氧的反应性降低，并减弱中枢神经系统（CNS）的化学感受转导，这两者共同作用可能导致慢性低氧时低氧通气反应（HVR）降低。在本研究中，我们试图确定内源性多巴胺的中枢或外周活性是否调节这种降低的HVR。我们研究了外周和中枢多巴胺受体阻断对对照组以及暴露于5500米模拟海拔3周的猫的HVR和颈动脉窦神经（CNS）对低氧的反应的影响。多潘立酮使低氧猫的颈动脉窦神经对低氧的反应增加到与对照组相似的水平。多潘立酮也使低氧猫的HVR增强，但仍低于对照组。结果，低氧动物的CNS化学感受转导仍然降低。我们进一步用氟哌啶醇治疗动物。然而，多潘立酮和氟哌啶醇联合治疗并未使低氧猫的颈动脉窦神经或通气对低氧的反应，或CNS化学感受转导进一步增加。因此，低氧猫的HVR降低既由主要为多巴胺能的颈动脉体低氧敏感性降低介导，也由必然涉及非多巴胺能机制的CNS化学感受转导降低介导。
