McKinley M J, Albiston A L, Allen A M, Mathai M L, May C N, McAllen R M, Oldfield B J, Mendelsohn F A O, Chai S Y
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Melbourne 3010, Vic., Australia.
Int J Biochem Cell Biol. 2003 Jun;35(6):901-18. doi: 10.1016/s1357-2725(02)00306-0.
Angiotensinogen, the precursor molecule for angiotensins I, II and III, and the enzymes renin, angiotensin-converting enzyme (ACE), and aminopeptidases A and N may all be synthesised within the brain. Angiotensin (Ang) AT(1), AT(2) and AT(4) receptors are also plentiful in the brain. AT(1) receptors are found in several brain regions, such as the hypothalamic paraventricular and supraoptic nuclei, the lamina terminalis, lateral parabrachial nucleus, ventrolateral medulla and nucleus of the solitary tract (NTS), which are known to have roles in the regulation of the cardiovascular system and/or body fluid and electrolyte balance. Immunohistochemical and neuropharmacological studies suggest that angiotensinergic neural pathways utilise Ang II and/or Ang III as a neurotransmitter or neuromodulator in the aforementioned brain regions. Angiotensinogen is synthesised predominantly in astrocytes, but the processes by which Ang II is generated or incorporated in neurons for utilisation as a neurotransmitter is unknown. Centrally administered AT(1) receptor antagonists or angiotensinogen antisense oligonucleotides inhibit sympathetic activity and reduce arterial blood pressure in certain physiological or pathophysiological conditions, as well as disrupting water drinking and sodium appetite, vasopressin secretion, sodium excretion, renin release and thermoregulation. The AT(4) receptor is identical to insulin-regulated aminopeptidase (IRAP) and plays a role in memory mechanisms. In conclusion, angiotensinergic neural pathways and angiotensin peptides are important in neural function and may have important homeostatic roles, particularly related to cardiovascular function, osmoregulation and thermoregulation.
血管紧张素原是血管紧张素I、II和III的前体分子,肾素、血管紧张素转换酶(ACE)以及氨肽酶A和N这些酶均可在脑内合成。血管紧张素(Ang)的AT(1)、AT(2)和AT(4)受体在脑内也大量存在。AT(1)受体见于多个脑区,如下丘脑室旁核和视上核、终板、外侧臂旁核、延髓腹外侧以及孤束核(NTS),已知这些脑区在心血管系统调节和/或体液及电解质平衡中发挥作用。免疫组织化学和神经药理学研究提示,在上述脑区,血管紧张素能神经通路利用血管紧张素II和/或血管紧张素III作为神经递质或神经调质。血管紧张素原主要在星形胶质细胞中合成,但血管紧张素II生成或整合入神经元以作为神经递质利用的过程尚不清楚。在某些生理或病理生理条件下,中枢给予AT(1)受体拮抗剂或血管紧张素原反义寡核苷酸可抑制交感神经活动并降低动脉血压,同时还会扰乱饮水和钠食欲、血管加压素分泌、钠排泄、肾素释放及体温调节。AT(4)受体与胰岛素调节的氨肽酶(IRAP)相同,在记忆机制中发挥作用。总之,血管紧张素能神经通路和血管紧张素肽在神经功能中很重要,可能具有重要的稳态作用,尤其是与心血管功能、渗透调节和体温调节相关。