Eisenhofer G, Saigusa T, Esler M D, Cox H S, Angus J A, Dorward P K
Baker Medical Research Institute, Prahran, Victoria, Australia.
Am J Physiol. 1991 Apr;260(4 Pt 2):R824-32. doi: 10.1152/ajpregu.1991.260.4.R824.
Peripheral- and central nervous system (CNS)-mediated effects of desipramine (Des) on sympathetic nerves and the contribution of alpha 2-adrenoceptors to these effects were studied in conscious rabbits. Blood pressure, renal sympathetic nerve activity (SNA), and norepinephrine (NE) reuptake and spillover into plasma were measured before and after intracisternal (ic) or intravenous (i.v.) administration of Des. In other animals, NE spillover responses to i.v. Des were examined before and after alpha 2-adrenoceptor blockade with i.v. idazoxan. Treatment with i.v. Des blocked neuronal reuptake and decreased renal SNA but did not alter blood pressure or NE spillover. Decreased NE release by sympathetic nerves after i.v. Des was reflected by a decrease in the combined rate of NE reuptake and spillover. Treatment with ic Des (at 1.7% of the i.v. dose) decreased blood pressure and renal SNA and produced equivalent falls in NE reuptake and spillover, indicating little peripheral effect of centrally administered Des on the efficiency of neuronal reuptake. Thus Des had two distinct actions: the drug blocked neuronal reuptake by direct actions on nerve endings and reduced SNA by actions within the CNS. After ic Des, decreased SNA produced parallel falls in NE reuptake, spillover, and blood pressure. After i.v. Des, blockade of neurotransmitter reuptake increased NE concentrations at sympathoeffector junctions offsetting the fall in SNA, so that there was little change in NE spillover or blood pressure. However, after alpha 2-adrenoceptor blockade with i.v. idazoxan, NE spillover increased in response to i.v. Des. Thus the Des-induced decrease in NE release was partly mediated by an action of raised intrasynaptic NE concentrations on inhibitory alpha 2-adrenoceptors.
在清醒兔中研究了去甲丙咪嗪（Des）对交感神经的外周和中枢神经系统（CNS）介导的作用，以及α2-肾上腺素受体对这些作用的贡献。在脑池内（ic）或静脉内（i.v.）给予Des之前和之后，测量血压、肾交感神经活动（SNA）以及去甲肾上腺素（NE）向血浆中的再摄取和溢出。在其他动物中，在用静脉注射咪唑克生进行α2-肾上腺素受体阻断之前和之后，检查静脉注射Des后的NE溢出反应。静脉注射Des治疗可阻断神经元再摄取并降低肾SNA，但不改变血压或NE溢出。静脉注射Des后交感神经释放NE减少表现为NE再摄取和溢出的合并速率降低。脑池内给予Des（静脉注射剂量的1.7%）治疗可降低血压和肾SNA，并使NE再摄取和溢出产生同等程度的下降，表明中枢给予的Des对神经元再摄取效率的外周作用很小。因此，Des有两种不同的作用：该药物通过直接作用于神经末梢阻断神经元再摄取，并通过中枢神经系统内的作用降低SNA。脑池内给予Des后，SNA降低导致NE再摄取、溢出和血压平行下降。静脉注射Des后，神经递质再摄取的阻断增加了交感效应器连接处的NE浓度，抵消了SNA的下降，因此NE溢出或血压几乎没有变化。然而，在用静脉注射咪唑克生进行α2-肾上腺素受体阻断后，静脉注射Des会使NE溢出增加。因此，Des诱导的NE释放减少部分是由突触内NE浓度升高对抑制性α2-肾上腺素受体的作用介导的。
