高血压与肾脏疾病中肾脏局部肾素-血管紧张素系统的激活及病理生理作用

摘要/Abstract

摘要： 肾脏存在独立调节的肾素-血管紧张素系统(RAS)。多数高血压与肾脏疾病患者均存在肾脏RAS 活性的上调, 这对维持机体水钠平衡有重要作用, 但同时也促进了高血压的发生, 并加速了肾损害的进展。本文结合最近一些基础及临床研究结果, 着重讨论疾病状态下肾脏RAS 激活的机制、后果及RAS 阻断剂的干预意义, 这对认识肾脏局部RAS 功能, 探讨延缓慢性肾脏病进展的治疗策略具有重要意义。

关键词: 肾素-血管紧张素系统, 高血压, 肾素-血管紧张素系统阻断剂, 肾脏疾病

Abstract: There is an independent-regulated renin- angiotensin system (RAS)in kidney.Most of patients with hypertension or kidney diseases present increased renal RAS activity, which maintains body water and sodium balance, but contributes to the occurrence of hypertension and renal damage progression.The article reviewes some recent basic and clinical researches, focusing on the renal RAS activation mechanisms, consequences and clinical significance of the intervention of RAS blockers, which may help us recognize local RAS function of kidney, explore the treatment strategies to control hypertension and slow chronic kidney disease progression.

Key words: renin-angiotensin system, hypertension, angiotensin converting enzyme inhibitor, kidney disease

中图分类号:

曹锦秀, 张丽萍, 高春林, 贾俊亚. 高血压与肾脏疾病中肾脏局部肾素-血管紧张素系统的激活及病理生理作用[J]. 中国临床药理学与治疗学, 2009, 14(12): 1436-1440.

CAO Jin-xiu, ZHANG Li-ping, GAO Chun-lin, JIA Jun-ya. Patho-physiological function of activiated renal renin-angiotensin system in hypertension and kidney disease[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(12): 1436-1440.

参考文献

[1] 贾俊亚, 丁国华.肾脏中肾素-血管紧张素系统的生理和病理生理作用[J].生理科学进展, 2008, 39(1):71-74.
[2] Sadjadi J, Kramer G, Yu C, et al.Angiotensin converting enzyme-independent angiotensin II production by chymase is up-regulated in the ischemic kidney in renovascular hypertension[J].J Surg Res, 2005, 127(2):65-69.
[3] Lavoie JL, Lake-Bruse KD, Sigmund CD.Increased blood pressure in transgenic mice expressing both human renin and angiotensinogen in the renal proximal tubule[J].Am J Physiol Renal, 2004, 286(5):F965-F971.
[4] Prieto-Carrasquero MC, Botros FT, Pagan J, et al.Collecting duct renin is upregulated in both kidneys of 2-kidney, 1-clip goldblatt hypertensive rats[J].Hypertension, 2008, 51(6):1590-1596.
[5] Kobori H, Nishiyama A, Harrison-Bernard LM, et al.Urinary angiotensinogen as an indicator of intrarenal angiotensin status in hypertension[J].Hypertension, 2004, 41(1):42-49.
[6] Prieto-Carrasquero MC, Kobori H, Qzawa Y, et al.AT1 receptor-mediated enhancement of collecting duct renin in angiotensin II-dependent hypertensive rats[J].Am J Physiol, 2005, 289(3):F632-F637.
[7] 贾俊亚, 丁国华, 陈铖, 等.血管紧张素Ⅱ 灌注诱导大鼠肾脏血管紧张素转换酶2 表达改变[J].中华肾脏病杂志, 2007, 23(7):458-463.
[8] Kobori H, Ozawa Y, Suzaki Y, et al.Enhanced intrarenal angiotensinogen contributes to early renal injury in spontaneously hypertensive rats[J].J Am Soc Nephrol, 2005, 16(10):2073-2080.
[9] Jaimes EA, ZhouMS, Pearse DD, et al.Upregulation of cortical COX-2 in salt-sensitive hypertension:role of angiotensin II and reactive oxygen species[J].Am J Physiol Renal Physiol, 2008, 294(2):F385-392.
[10] Navar LG, Nishiyama A.Why are angiotensin concentrations so high in the kidney[J] ? Curr Opin Nephrol Hypertens, 2004, 13(1):10-15.
[11] Kobori H, Katsurada A, Ozawa Y, et al.Enhanced intrarenal oxidative stress and angiotensinogen in IgA nephropathy patients[J].Biochem Biophys Res Commun, 2007, 358(1):156-163.
[12] Chan LY, Leung JC, Tang SC, et al.Tubular expression of angiotensin II receptors and their regulation in IgA nephropathy[J].J Am Soc Nephrol, 2005, 16(10):2306-2317.
[13] Xiao J, Leung JC, Chan LY, et al.Protective effect of peroxisome proliferator-activated receptor-gamma agonists on activated renal proximal tubular epithelial cells in IgA nephropathy[J].Nephrol Dial Transplant, 2009, 24(7): 2067-2077.
[14] Mezzano SA, Aros CA, Droguett A, et al.Renal angiotensin II up-regulation and myofibroblast activation in human membranous nephropathy[J].Kidney Int, 2003, 64(S1):S39-S45.
[15] Shin GT, Kim WH, Yim H, et al.Effects of suppressing intrarenal angiotensinogen on renal transforming growth factor-beta1 expression in acute ureteral obstruction[J]. Kidney Int, 2005, 67(3):897-908.
[16] Wu MS, Yang CW, Chang CT, et al.Cyclosporin increases the density of angiotensin II subtype 1 (AT1) receptors in mouse medullary thick ascending limb cells[J]. Nephrol Dial Transplant, 2003, 18(10):1458-1465.
[17] Iijima K, Hamahira K, Kobayashi A, et al.Immunohistochemical analysis of renin activity in chronic cyclosporine nephropathy in childhood nephrotic syndrome[J].J Am Soc Nephrol, 2003, 11(11):2265-2271.
[18] Loghman-Adham M, Soto CE, Inagami T, et al.The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease[J].Am J Physiol, 2004, 287(5):F775-F788.
[19] Kelly DJ, Skinner SL, Gilbert RE, et al.Effects of endothelin or angiotensin II receptor blockade on diabetes in the transgenic (mRen-2)27 rat[J].Kidney Int, 2000, 57(10):1882-1894.
[20] Sharma R, Sharma M, Reddy S, et al.Chronically increased intrarenal angiotensin II causes nephropathy in an animal model of type 2 diabetes[J].Front Biosci, 2006, 11(4):968-976.
[21] Huang XR, Chen WY, Truong LD, et al.Chymase is upregulated in diabetic nephropathy:implications for an alternative pathway of angiotensin II-mediated diabetic renal and vascular disease[J].J Am Soc Nephrol, 2003, 14(9):1738-1747.
[22] Fliser D, Wagner KK, Loos A, et al.Chronic angiotensin II receptor blockade reduces (intra)renal vascular resistance in patients with type 2 diabetes[J].J Am Soc Nephrol, 2005, 16(7):1135-1140.
[23] Faraggiana T, Venkataseshan VS, Inagami T, et al.Immunohistochemical localization of renin in end-stage kidneys[J].Am J Kidney Dis, 1998, 12(1):194-199.
[24] Mann JF, Schmieder RE, McQueen M, et al.Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study):A multicentre, randomised, double-blind, controlled trial[J].Lancet, 2008, 372(2):547-553.
[25] Berns JS.Is angiotensin-converting enzyme inhibitor and angiotensin receptor blocker combination therapy better than monotherapy and safe in patients with CKD[J] ? Am J Kidney Dis, 2009, 53(2):192-196.
[26] Mehdi UF, Adams-Huet B, Raskin P, et al.Addition of angiotensin receptor blockade or mineralocorticoid antagonism to maximal angiotensin-converting enzyme inhibition in diabetic nephropathy[J].Am Soc Nephrol, 2009 Nov 19.PMID:19926893 [Epub ahead of print] [27] Fan YY, Baba R, Nagai Y, et al.Augmentation of intrarenal angiotensin II levels in uninephrectomized aldosterone salt-treated hypertensive rats;renoprotective effects of an ultrahigh dose of olmesartan[J].Hypertens Res, 2006, 29(1):169-178.