Shan J, Krukoff T L
Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
J Neuroendocrinol. 2000 Aug;12(8):802-10. doi: 10.1046/j.1365-2826.2000.00524.x.
Adrenomedullin (ADM) is a potent vasodilator in the periphery which also acts centrally to increase blood pressure and inhibit drinking, feeding and salt appetite. This study was designed to study the effects of circulating ADM on neuronal activation in autonomic centres in the rat brain and to examine whether neuronal nitric oxide (NO) may participate in these processes. We identified activated neurones 1 h after intravenous (i.v.) injections of ADM (2 nmol/kg) using immunohistochemistry for Fos. The nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemical reaction was used to localize putative NO-producing neurones and double labelling for Fos and NADPH-d was used to identify activated NO producing neurones. To separate baroreceptor-induced neuronal activation in autonomic centres by ADM from other effects which it may have, i.v. infusions of sodium nitroprusside (NP) were used to mimic the hypotensive effects of ADM in control rats. Significantly greater numbers of activated neurones were found in the paraventricular nucleus of the hypothalamus (PVN) and especially in the dorsolateral medial parvocellular division, the nucleus of the solitary tract, and the area postrema (AP) of ADM-treated rats compared to control rats. In addition, the number of activated NO-producing neurones in the PVN was significantly higher in ADM-treated rats compared to rats treated with NP. To determine whether AP is one of the possible routes through which systemic ADM enters the brain to exert its central effects, the APs of rats were ablated by aspiration. One hour after i.v. injections of ADM, significantly fewer PVN neurones were activated in AP ablation rats compared to AP sham ablation rats. Similarly, the number of activated NO-producing neurones in the PVN was significantly lower in AP ablation rats compared to AP sham ablation rats. In conclusion, our results suggest that systemic ADM gains access to the brain through the AP to regulate neuronal activity in autonomic centres and that neuronal NO might be involved in central autonomic and/or neuroendocrine regulation by ADM.
肾上腺髓质素（ADM）在外周是一种强效血管舒张剂，在中枢也发挥作用，可升高血压并抑制饮水、进食和盐欲。本研究旨在探讨循环ADM对大鼠脑内自主神经中枢神经元激活的影响，并研究神经元型一氧化氮（NO）是否参与这些过程。我们通过Fos免疫组化法，在静脉注射ADM（2 nmol/kg）1小时后鉴定激活的神经元。采用烟酰胺腺嘌呤二核苷酸磷酸黄递酶（NADPH-d）组织化学反应来定位假定的产生NO的神经元，并使用Fos和NADPH-d的双重标记来鉴定激活的产生NO的神经元。为了将ADM在自主神经中枢引起的压力感受器诱导的神经元激活与它可能具有的其他效应区分开来，静脉输注硝普钠（NP）以模拟ADM对对照大鼠的降压作用。与对照大鼠相比，在ADM处理的大鼠的下丘脑室旁核（PVN），特别是背外侧内侧小细胞部、孤束核和最后区（AP）中发现了数量明显更多的激活神经元。此外，与NP处理的大鼠相比，ADM处理的大鼠PVN中激活的产生NO的神经元数量明显更高。为了确定AP是否是全身ADM进入脑内发挥其中枢作用的可能途径之一，通过抽吸切除大鼠的AP。静脉注射ADM 1小时后，与AP假切除大鼠相比，AP切除大鼠中被激活的PVN神经元明显减少。同样，与AP假切除大鼠相比，AP切除大鼠PVN中激活的产生NO的神经元数量明显更低。总之，我们的结果表明，全身ADM通过AP进入脑内以调节自主神经中枢的神经元活动，并且神经元NO可能参与ADM的中枢自主神经和/或神经内分泌调节。
