血管紧张素(1-7)的神经活性研究进展

doi:10.12092/j.issn.1009-2501.2018.12.019

摘要/Abstract

摘要：

血管紧张素(1-7)［angiotensin(1-7),Ang(1-7)］通过肾素-血管紧张素系统(renin-angiotensin system,RAS)新的作用分支血管紧张素转化酶2(angiotensin-converting enzyme 2,ACE2)-血管紧张素(1-7)-Mas受体(ACE2-Ang(1-7)-Mas)轴反向调节经典ACE-AngII-AT受体轴。Ang(1-7)广泛存在于下丘脑视上核和室旁核，可以通过缓激肽、一氧化氮合酶(NOS)、环氧合酶(COX)及一些信号通路影响其他中枢神经递质的合成及释放，发挥扩张血管、抗心律失常、抗炎等作用，达到保护心血管及中枢神经系统的效果。本文就Ang(1-7)的分布及在中枢神经系统中多样性的生物功能作一综述。

关键词: 血管紧张素(1-7), 肾素-血管紧张素系统, 反向调节, 中枢神经系统

Abstract:

Angiotensin (1-7) reverse regulation of the classic ACE-AngII-AT axis through the branch of the new role of angiotensin converting enzyme ACE2-Ang (1-7) -Mas receptor axis. Ang (1-7) is widely distributed in the supraoptic and paraventricular nucleus of hypothalamus. It has effects of dilating blood vessels, anti-arrhythmia, anti-inflammatory and so on, which could protect the cardiovascular and central nervous system by affecting the synthesis and releasing other central neurotransmitters through bradykinin, nitric oxide synthase (NOS), cyclooxygenase (COX) and some signaling pathways. This paper reviews the distribution of Ang (1-7) and the diversity of the biological functions in the central nervous system.

Key words: angiotensin(1-7), renin-angiotensin system, reverse regulation, central nervous system

中图分类号:

陈丹，郭玉金，杨梦琦，蔡骅琳，江沛. 血管紧张素(1-7)的神经活性研究进展[J]. 中国临床药理学与治疗学, 2018, 23(12): 1425-1430.

CHEN Dan, GUO Yujin, YANG Mengqi, CA Hualin, JIANG Pei. Advances in studies of neurotoxicity of angiotensin(1-7)[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(12): 1425-1430.

参考文献

［1］Yu X, Cui L, Hou F, et al. Angiotensin-converting enzyme 2-angiotensin (1-7)-Mas axis prevents pancreatic acinar cell inflammatory response via inhibition of the p38 mitogen-activated protein kinase/nuclear factor-κB pathway［J］. Int J Mol Med, 2018, 41(1): 409-420.
［2］Block CH, Santos RA, Brosnihan KB, et al. Immunocytochemical localization of angiotensin-(1-7) in the rat forebrain［J］. Peptides, 1988, 9(6): 1395-1401.
［3］Arnold AC, Sakima A, Kasper SO, et al. The brain renin-angiotensin system and cardiovascular responses to stress: insights from transgenic rats with low brain angiotensinogen ［J］. J Appl Physiol, 2012, 113(12): 1929-1936.
［4］Chappell MC, Brosnihan KB, Diz DI, et al. Identification of angiotensin-(1-7) in rat brain. Evidence for differential processing of angiotensin peptides ［J］. J Biol Chem, 1989, 264(28): 16518-16523.
［5］Pereira MG, Souza LL, Becari C, et al. Angiotensin II-independent angiotensin-(1-7) formation in rat hippocampus: involvement of thimet oligopeptidase［J］. Hypertension, 2013, 62(5): 879-885.
［6］Gouveia TL, Frangiotti MI, de Brito JM, et al. The levels of renin-angiotensin related components are modified in the hippocampus of rats submitted to pilocarpine model of epilepsy ［J］. Neurochem Int, 2012, 61(1): 54-62.
［7］Xing J, Kong J, Lu J, et al. Angiotensin-(1-7) inhibits neuronal activity of dorsolateral periaqueductal gray via a nitric oxide pathway ［J］. Neurosci Lett, 2012, 522(2): 156-161.
［8］Yang RF, Yin JX, Li YL, et al. Angiotensin-(1-7) increases neuronal potassium current via a nitric oxide-dependent mechanism ［J］. Am J Physiol Cell Physiol, 2011, 300(1): C58-64.
［9］Lopez Verrilli MA, Rodriguez Fermepín M, Longo Carbajosa N, et al. Angiotensin-(1-7) through Mas receptor up-regulates neuronal norepinephrine transporter via Akt and Erk1/2-dependent pathways ［J］. J Neurochem, 2012, 120(1): 46-55.
［10］Lei Y, Xu Q, Zeng B, et al. Ang(1-7) protects cardiomyocytes against HG-induced injuries through inhibiting ROS-activated leptin-p38 MAPK/ERK1/2 pathways but not leptin-JNK pathway in vitro ［J］. J Diab Invest, 2017, 8.
［11］Zheng JL, Li GZ, Chen SZ, et al. Angiotensin converting enzyme 2/Ang(1-7)/mas axis protects brain from ischemic injury with a tendency of age-dependence ［J］. CNS Neurosci Therap, 2014, 20(5): 452-459.
［12］Wu ZT, Ren CZ, Yang YH, et al. The PI3K signaling-mediated nitric oxide contributes to cardiovascular effects of angiotensin-(1-7) in the nucleus tractus solitarii of rats ［J］. Nitric Oxide, 2016, 52: 56-65.
［13］Sriramula S, Xia H, Xu P, et al. Brain-targeted Angiotensin-converting enzyme 2 overexpression attenuates neurogenic hypertension by inhibiting cyclooxygenase-mediated inflammation［J］. Hypertension, 2015, 65(3): 577-586.
［14］Couto AS, Baltatu O, Santos RA, et al. Differential effects of angiotensin II and angiotensin-(1-7) at the nucleus tractus solitarii of transgenic rats with low brain angiotensinogen ［J］. J Hyper, 2002, 20(5): 919-925.
［15］Oliveira DR, Santos RA, Santos GF, et al. Changes in the baroreflex control of heart rate produced by central infusion of selective angiotensin antagonists in hypertensive rats ［J］. Hypertension, 1996, 27(6): 1284-1290.
［16］Nautiyal M, Shaltout HA, de Lima DC, et al. Central angiotensin-(1-7) improves vagal function independent of blood pressure in hypertensive (mRen2)27 rats ［J］. Hypertension, 2012, 60(5): 1257-1265.
［17］Garcia-Espinosa MA, Shaltout HA, Gallagher PE, et al. In vivo expression of angiotensin-(1-7) lowers blood pressure and improves baroreflex function in transgenic (mRen2)27 rats ［J］. J Cardiovas Pharmacol, 2012, 60(5): 150-157.
［18］Shaltout HA, Rose JC, Chappell MC, et al. Angiotensin-(1-7) deficiency and baroreflex impairment precede the antenatal Betamethasone exposure-induced elevation in blood pressure ［J］. Hypertension, 2012, 59(2): 453-458.
［19］Marshall AC, Shaltout HA, Nautiyal M, et al. Fetal betamethasone exposure attenuates angiotensin-(1-7)-Mas receptor expression in the dorsal medulla of adult sheep ［J］. Peptides, 2013, 44(6): 25-31.
［20］Gironacci MM, Longo Carbajosa NA, Goldstein J, et al. Neuromodulatory role of angiotensin-(1-7) in the central nervous system ［J］. Clin Sci, 2013, 125(2): 57-65.
［21］Lazaroni TL, Raslan AC, Fontes WR, et al. Angiotensin-(1-7)/Mas axis integrity is required for the expression of object recognition memory ［J］. Neurobiol Learn Memory, 2012, 97(1): 113-123.
［22］Hay M, Vanderah TW, Samareh-Jahani F, et al. Cognitive impairment in heart failure: A protective role for Angiotensin-(1-7) ［J］. Behav Neurosci, 2017, 131(1): 99-114.
［23］Bild W, Ciobica A. Angiotensin-(1-7) central administration induces anxiolytic-like effects in elevated plus maze and decreased oxidative stress in the amygdala ［J］. J Affect Dis, 2013, 145(2): 165-171.
［24］Mecca AP, Regenhardt RW, O'Connor TE, et al. Cerebroprotection by angiotensin-(1-7) in endothelin-1-induced ischaemic stroke ［J］. Exp Physiol, 2011, 96(10): 1084-1096.
［25］Regenhardt RW, Desland F, Mecca AP, et al. Anti-inflammatory effects of angiotensin-(1-7) in ischemic stroke ［J］. Neuropharmacol, 2013, 71(4): 154-163.
［26］Skiba DS, Nosalski R, Mikolajczyk TP, et al. Antiatherosclerotic effect of Ang(1-7) non-peptide mimetic (AVE 0991) is mediated by inhibition of perivascular and plaque inflammation in early atherosclerosis ［J］. Brit J Pharmacol, 2016.
［27］Oliveira-Lima OC, Pinto MCX, Johan D, et al. Mas receptor deficiency exacerbates lipopolysaccharide-induced cerebral and systemic inflammation in mice［J］. Immunobiol, 2015, 220(12): 1311-1321.
［28］Jiang T, Gao L, Guo J, et al. Suppressing inflammation by inhibiting the NF-κB pathway contributes to the neuroprotective effect of angiotensin-(1-7) in rats with permanent cerebral ischaemia［J］. Brit J Pharmacol, 2012, 167(7): 1520-1532.
［29］Jiang T, Yu JT, Zhu XC, et al. Angiotensin-(1-7) induces cerebral ischaemic tolerance by promoting brain angiogenesis in a Mas/eNOS-dependent pathway ［J］. Brit J Pharmacol, 2014, 171(18): 4222-4232.
［30］Li H, Liu X, Ren Z, et al. Effects of Diabetic Hyperglycemia on Central Ang(1-7)-Mas-R-nNOS Pathways in Spontaneously Hypertensive Rats［J］. Cell Physiol Biochem, 2016, 40(5): 1186-1197.
［31］Regenhardt RW, Mecca AP, Desland F, et al. Centrally administered angiotensin-(1-7) increases the survival of stroke-prone spontaneously hypertensive rats ［J］. Exp Physiol, 2014, 99(2): 442-453.
［32］Shimada K, Furukawa H, Wada K, et al. Angiotensin-(1-7) protects against the development of aneurysmal subarachnoid hemorrhage in mice ［J］. J Cere Blood Flow Metab, 2015, 9(7): 1163-1168.
［33］Cheng Y, Li Q, Zhang Y, et al. Effects of female sex hormones on expression of the Ang(1-7)/Mas-R/nNOS pathways in rat brain ［J］. Can J Physiol Pharmacol, 2015, 93(11): 993-998.
［34］Goldstein J, Carden T, Perez MJ, et al. Angiotensin-(1-7) protects from brain damage induced by shiga toxin 2-producing enterohemorrhagic Escherichia coli ［J］. Am J Physiol Regul Integr Comp Physiol, 2016, 311(6): R1173-R1185.
［35］Lu J, Jiang T, Wu L, et al. The expression of angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor axis are upregulated after acute cerebral ischemic stroke in rats ［J］. Neuropeptides, 2013, 47(5): 289-295.
［36］Teng J, Li G, Shi J, et al. Angiotensin-(1-7) modulates renin-angiotensin system associated with reducing oxidative stress and attenuating neuronal apoptosis in the brain of hypertensive rats［J］. Pharmacol Res, 2012, 67(1): 84-93.
［37］Jiang T, Gao L, Zhu X C, et al. Angiotensin-(1-7) inhibits autophagy in the brain of spontaneously hypertensive rats［J］. Pharmacological Research the Official Journal of the Italian Pharmacol Soc, 2013, 71(5): 61-68.
［38］Ren CZ, Yang YH, Sun JC, et al. Exercise training improves the altered renin-angiotensin system in the rostral ventrolateral medulla of hypertensive rats ［J］. Ox Med Cell Long, 2016, 2016(5): 1-11.
［39］Wang Y, Shoemaker R, Powell D, et al. Differential effects of mas receptor deficiency on cardiac function and blood pressure in obese male and female mice ［J］. Am J Physiol Regul Integr Comp Physiol, 2016.
［40］Foureaux G, Nogueira BS, Coutinho DCO, et al. Activation of endogenous angiotensin converting enzyme 2 prevents early injuries induced by hyperglycemia in rat retina ［J］. Braz J Med Biol Res, 2015, 48(12): 1109-1114.

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