Shi Peng, Martinez Michelle A, Calderon Alfredo S, Chen Qinghui, Cunningham J Thomas, Toney Glenn M
Department of Physiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
J Physiol. 2008 Nov 1;586(21):5231-45. doi: 10.1113/jphysiol.2008.159665. Epub 2008 Aug 28.
Body fluid hyperosmolality has long been known to elicit homeostatic responses that range from drinking to inhibition of salt appetite to release of neurohypohyseal hormones (i.e. vasopressin and oxytocin). More recently, it has been recognized that hyperosmolality is capable of also provoking a significant increase of sympathetic nerve activity (SNA). It has been reported that neurones in the forebrain organum vasculosum laminae terminalis (OVLT) and hypothalamic paraventricular nucleus (PVN) each contribute significantly to this response. Here we sought to determine if sympathoexcitatory levels of hyperosmolality activate specifically those OVLT neurones that form a monosynaptic pathway to the PVN. First, we established in anaesthetized rats that graded concentrations of hypertonic NaCl (1.5 and 3.0 osmol kg(-1)) elicit graded increases of renal SNA (RSNA) when infused at a rate of 0.1 ml min(-1) through an internal carotid artery (ICA) - the major vascular supply of the forebrain. Next, infusions were performed in conscious rats in which OVLT neurones projecting to the PVN (OVLT-PVN) were retrogradely labelled with cholera toxin subunit B (CTB). Immunostaining of the immediate early gene product Fos and CTB was performed to quantify osmotic activation of OVLT-PVN neurones. ICA infusions of hypertonic NaCl and mannitol each significantly (P < 0.01-0.001) increased the number of Fos immunoreactive (Fos-ir) neuronal nuclei in the dorsal cap (DC) and lateral margins (LM) of OVLT. In the LM, infusions of 1.5 and 3.0 osmol kg(-1) NaCl produced similar increases in the number of Fos-ir neurones. In the DC, these infusions produced graded increases in Fos expression. Among OVLT neurones with axons projecting directly to the PVN (i.e. CTB-ir), graded hypertonic NaCl infusions again produced graded increases in Fos expression and this was observed in both the DC and LM. Although the DC and LM contained a similar number of OVLT-PVN neurones, the proportion of such neurones that expressed Fos-ir in responses to ICA hypertonic NaCl infusions was greater in the DC (P < 0.001). These findings support the conclusion that PVN-projecting neurones in the DC and LM of OVLT could participate in behavioural, neuroendocrine, and sympathetic nervous system responses to body fluid hyperosmolality.
长期以来,人们都知道体液高渗会引发一系列稳态反应,这些反应包括饮水、抑制盐食欲以及释放神经垂体激素(即血管加压素和催产素)。最近,人们认识到高渗还能够显著增加交感神经活动(SNA)。据报道,前脑终板血管器(OVLT)和下丘脑室旁核(PVN)中的神经元对此反应均有显著贡献。在此,我们试图确定高渗引起的交感兴奋水平是否会特异性激活那些形成至PVN单突触通路的OVLT神经元。首先,我们在麻醉大鼠中证实,以0.1 ml min⁻¹的速率通过颈内动脉(ICA,前脑的主要血管供应)输注不同浓度的高渗NaCl(1.5和3.0 osmol kg⁻¹)会引起肾交感神经活动(RSNA)的分级增加。接下来,对清醒大鼠进行输注,其中将投射至PVN的OVLT神经元(OVLT-PVN)用霍乱毒素B亚基(CTB)进行逆行标记。对即刻早期基因产物Fos和CTB进行免疫染色,以量化OVLT-PVN神经元的渗透激活情况。通过ICA输注高渗NaCl和甘露醇均显著(P < 0.01 - 0.001)增加了OVLT背帽(DC)和外侧边缘(LM)中Fos免疫反应性(Fos-ir)神经元核的数量。在LM中,输注1.5和3.0 osmol kg⁻¹ NaCl使Fos-ir神经元数量产生相似的增加。在DC中,这些输注使Fos表达呈分级增加。在轴突直接投射至PVN的OVLT神经元(即CTB-ir)中,分级输注高渗NaCl再次使Fos表达呈分级增加,且在DC和LM中均观察到这一现象。尽管DC和LM中OVLT-PVN神经元数量相似,但在对ICA输注高渗NaCl的反应中,DC中表达Fos-ir的此类神经元比例更高(P < 0.001)。这些发现支持以下结论:OVLT的DC和LM中投射至PVN的神经元可能参与对体液高渗的行为、神经内分泌和交感神经系统反应。