Sunn N, McKinley M J, Oldfield B J
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Melbourne, Victoria, Australia.
J Neuroendocrinol. 2003 Aug;15(8):725-31. doi: 10.1046/j.1365-2826.2003.00969.x.
The aim of this study was to determine, in conscious rats, whether elevated concentrations of circulating angiotensin II activate neurones in both the subfornical organ and organum vasculosum of the lamina terminalis (OVLT) that project to the bed nucleus of the stria terminalis (BNST). The strategy employed was to colocalize retrogradely transported cholera toxin B subunit (CTB) from the BNST, with elevated levels of Fos protein in response to angiotensin II. Circulating angiotensin II concentrations were increased by either intravenous infusion of angiotensin II or subcutaneous injection of isoproterenol. Neurones exhibiting Fos in response to angiotensin II were present in the subfornical organ, predominantly in its central core but with some also seen in its peripheral aspect, the dorsal and lateral margins of the OVLT, the supraoptic nucleus and the parvo- and magnocellular divisions of the paraventricular nucleus. Fos-labelling was not apparent in control rats infused with isotonic saline intravenously or injected with either CTB or CTB conjugated to gold particles (CTB-gold) only. Of the neurones in the subfornical organ that were shown by retrograde labelling to project to BNST, approximately 50% expressed Fos in response to isoproterenol. This stimulus also increased Fos in 33% of neurones in the OVLT that project to BNST. Double-labelled neurones were concentrated in the central core of the subfornical organ and lateral margins of the OVLT in response to increased circulating angiotensin II resulting from isoproterenol treatment. These data support a role for circulating angiotensin II acting either directly or indirectly on neurones in subfornical organ and OVLT that project to the BNST and provide further evidence of functional regionalization within the subfornical organ and the OVLT. The function of these pathways is yet to be determined; however, a role in body fluid homeostasis is possible.
本研究的目的是在清醒大鼠中确定,循环中血管紧张素II浓度升高是否会激活穹窿下器官和终板血管器(OVLT)中投射至终纹床核(BNST)的神经元。采用的策略是将从BNST逆行转运的霍乱毒素B亚基(CTB)与因血管紧张素II而升高的Fos蛋白水平进行共定位。通过静脉输注血管紧张素II或皮下注射异丙肾上腺素来提高循环中血管紧张素II的浓度。对血管紧张素II产生反应而表现出Fos的神经元存在于穹窿下器官中,主要在其中央核心,但在其周边部分、OVLT的背侧和外侧边缘、视上核以及室旁核的小细胞部和大细胞部也可见到一些。在仅静脉注射等渗盐水或仅注射CTB或与金颗粒偶联的CTB(CTB-金)的对照大鼠中,未观察到明显的Fos标记。在穹窿下器官中,经逆行标记显示投射至BNST的神经元中,约50%对异丙肾上腺素产生反应而表达Fos。这种刺激还使投射至BNST的OVLT中33%的神经元Fos增加。由于异丙肾上腺素治疗导致循环中血管紧张素II升高,双标记神经元集中在穹窿下器官的中央核心和OVLT的外侧边缘。这些数据支持循环中血管紧张素II直接或间接作用于投射至BNST的穹窿下器官和OVLT中的神经元,并为穹窿下器官和OVLT内的功能分区提供了进一步证据。这些通路的功能尚待确定;然而,它们可能在体液稳态中发挥作用。