Electrolyte Blood Press.  2008 Jun;6(1):42-50. 10.5049/EBP.2008.6.1.42.

Renin-Angiotensin System-Considerations for Hypertension and Kidney

• Yim HE
• Yoo KH

• KMID: 2052305
• DOI: http://doi.org/10.5049/EBP.2008.6.1.42

Abstract

The kidneys play a fundamental role in the long-term control of arterial pressure by regulating sodium balance and extracellular fluid volume. The renin-angiotensin system (RAS) is at the center of the regulation of hypertension and progressive renal injury. It has gradually become clear that not only systemic RAS, but also intrarenal RAS has specific effects in the pathogenesis and progression of hypertension and renal damage. All of the RAS components are exhibited in the kidney and intrarenal angiotensin II (Ang II) is formed by multiple mechanisms. The demonstration of much enhanced levels of Ang II within specific renal compartments points out selective local regulation of Ang II in the kidney, showing that intrarenal Ang II levels are regulated in a way different from circulating Ang II. The importance of the RAS in involving proper nephrogenesis is also well known, and suppression of the RAS during fetal development may play a key role in mediating the structural and physiological changes observed in models of fetal programming of hypertension.

MeSH Terms

Angiotensin II
Arterial Pressure
Blood Pressure
Extracellular Fluid
Fetal Development
Hypertension
Kidney
Negotiating
Renin-Angiotensin System
Sodium
Angiotensin II
Sodium

Figure

• 

  Fig. 1 Classic and alternative pathways of the renin-angiotensin system (RAS). Angiotensin converting enzyme (ACE), chymase, and ACE2 are involved in the production of angiotensin (Ang) II and Ang1-7. It seems that ACE and ACE2 have balancing functions by negatively regulating different RAS products. ATI, angiotensin II type 1; AT2, angiotensin II type 2.

Reference

1. Toke A, Meyer T. Wolf G, editor. Hemodynamic effects of angiotenin II in the kidney. The renin-angiotensin system and progression of renal diseases. 2001. 1st ed. Basel: Karger;p. 34–46.

2. Paul M, Poyan Mehr A, Kreutz R. Physiology of local renin-angiotensin systems. Physiol Rev. 2006; 86:747–803. PMID: 16816138.

3. Ichihara A, Kobori H, Nishiyama A, Navar LG. Renal renin-angiotensin system. Contrib Nephrol. 2004; 143:117–130. PMID: 15248360.

4. Petrie MC, Padmanabhan N, McDonald JE, Hillier C, Connell JM, McMurray JJ. Angiotensin converting enzyme (ACE) and non-ACE dependent angiotensin II generation in resistance arteries from patients with heart failure and coronary heart disease. J Am Coll Cardiol. 2001; 37:1056–1061. PMID: 11263608.

5. Brand M, Lamande N, Sigmund CD, Larger E, Corvol P, Gasc JM. Angiotensinogen modulates renal vasculature growth. Hypertension. 2006; 47:1067–1074. PMID: 16636191.

6. Takahashi N, Lopez ML, Cowhig JE Jr, Taylor MA, Hatada T, Riggs E, et al. Ren1c homozygous null mice are hypotensive and polyuric, but heterozygotes are indistinguishable from wild-type. J Am Soc Nephrol. 2005; 16:125–132. PMID: 15563565.

7. Woods LL, Ingelfinger JR, Nyengaard JR, Rasch R. Maternal protein restriction suppresses the newborn reninangiotensin system and programs adult hypertension in rats. Pediatr Res. 2001; 49:460–467. PMID: 11264427.

8. Vehaskari VM, Stewart T, Lafont D, Soyez C, Seth D, Manning J. Kidney angiotensin and angiotensin receptor expression in prenatally programmed hypertension. Am J Physiol Renal Physiol. 2004; 287:F262–F267. PMID: 15100095.

9. Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ. Weight in infancy and death from ischaemic heart disease. Lancet. 1989; 2:577–580. PMID: 2570282.

10. Brenner BM, Garcia DL, Anderson S. Glomeruli and blood pressure. Less of one, more the other? Am J Hypertens. 1988; 1:335–347. PMID: 3063284.

11. Yamamoto T, Hayashi K, Matsuda H, Kubota E, Tanaka H, Ogasawara Y, et al. In vivo visualization of angiotensin II- and tubuloglomerular feedback-mediated renal vasoconstriction. Kidney Int. 2001; 60:364–369. PMID: 11422773.

12. Harrison-Bernard LM, Cook AK, Oliverio MI, Coffman TM. Renal segmental microvascular responses to ANG II in AT1A receptor null mice. Am J Physiol Renal Physiol. 2003; 284:F538–F545. PMID: 12429556.

13. Whaley-Connell AT, Chowdhury NA, Hayden MR, Stump CS, Habibi J, Wiedmeyer CE, et al. Oxidative stress and glomerular filtration barrier injury: role of the reninangiotensin system in the Ren2 transgenic rat. Am J Physiol Renal Physiol. 2006; 291:F1308–F1314. PMID: 16788142.

14. Kobori H, Nangaku M, Navar LG, Nishiyama A. The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev. 2007; 59:251–287. PMID: 17878513.

15. Schnermann J. Micropuncture analysis of tubuloglomerular feedback regulation in transgenic mice. J Am Soc Nephrol. 1999; 10:2614–2619. PMID: 10589702.

16. Valles P, Wysocki J, Batlle D. Angiotensin II and renal tubular ion transport. ScientificWorldJournal. 2005; 5:680–690. PMID: 16142301.

17. Oliverio MI, Delnomdedieu M, Best CF, Li P, Morris M, Callahan MF, et al. Abnormal water metabolism in mice lacking the type 1A receptor for ANG II. Am J Physiol Renal Physiol. 2000; 278:F75–F82. PMID: 10644657.

18. Kang NS, Yim HE, Bae IS, Choi JH, Choi BM, Yoo KH, et al. ACE inhibition modulates transforming growth factor-beta receptors in the young rat. Pediatr Nephrol. 2003; 18:865–871. PMID: 12883979.

19. Lantelme P, Rohrwasser A, Gociman B, Hillas E, Cheng T, Petty G, et al. Effects of dietary sodium and genetic background on angiotensinogen and Renin in mouse. Hypertension. 2002; 39:1007–1014. PMID: 12019284.

20. Sachetelli S, Liu Q, Zhang SL, Liu F, Hsieh TJ, Brezniceanu ML, et al. RAS blockade decreases blood pressure and proteinuria in transgenic mice overexpressing rat angiotensinogen gene in the kidney. Kidney Int. 2006; 69:1016–1023. PMID: 16528251.

21. Nguyen G. The (pro)renin receptor: pathophysiological roles in cardiovascular and renal pathology. Curr Opin Nephrol Hypertens. 2007; 16:129–133. PMID: 17293688.

22. Oliver JA. Receptor-mediated actions of renin and prorenin. Kidney Int. 2006; 69:13–15. PMID: 16374416.

23. Metzger R, Bohle RM, Pauls K, Eichner G, Alhenc-Gelas F, Danilov SM, et al. Angiotensin-converting enzyme in non-neoplastic kidney diseases. Kidney Int. 1999; 56:1442–1454. PMID: 10504496.

24. Navar LG, Harrison-Bernard LM, Nishiyama A, Kobori H. Regulation of intrarenal angiotensin II in hypertension. Hypertension. 2002; 39:316–322. PMID: 11882566.

25. Li XC, Navar LG, Shao Y, Zhuo JL. Genetic deletion of AT1a receptors attenuates intracellular accumulation of ANG II in the kidney of AT1a receptor-deficient mice. Am J Physiol Renal Physiol. 2007; 293:F586–F593. PMID: 17537986.

26. Wei CC, Tian B, Perry G, Meng QC, Chen YF, Oparil S, et al. Differential ANG II generation in plasma and tissue of mice with decreased expression of the ACE gene. Am J Physiol Heart Circ Physiol. 2002; 282:H2254–H2258. PMID: 12003835.

27. Pendergrass KD, Averill DB, Ferrario CM, Diz DI, Chappell MC. Differential expression of nuclear AT1 receptors and angiotensin II within the kidney of the male congenic mRen2.Lewis rat. Am J Physiol Renal Physiol. 2006; 290:F1497–F1506. PMID: 16403834.

28. Komlosi P, Fuson AL, Fintha A, Peti-Peterdi J, Rosivall L, Warnock DG, et al. Angiotensin I conversion to angiotensin II stimulates cortical collecting duct sodium transport. Hypertension. 2003; 42:195–199. PMID: 12835330.

29. Siragy HM, Inagami T, Ichiki T, Carey RM. Sustained hypersensitivity to angiotensin II and its mechanism in mice lacking the subtype-2 (AT2) angiotensin receptor. Proc Natl Acad Sci U S A. 1999; 96:6506–6510. PMID: 10339618.

30. Sadjadi J, Kramer GL, Yu CH, BurressWelborn M 3rd, Chappell MC, Gregory Modrall J. Angiotensin converting enzyme-independent angiotensin ii production by chymase is up-regulated in the ischemic kidney in renovascular hypertension. J Surg Res. 2005; 127:65–69. PMID: 15869764.

31. Gurley SB, Allred A, Le TH, Griffiths R, Mao L, Philip N, et al. Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice. J Clin Invest. 2006; 116:2218–2225. PMID: 16878172.

32. Oudit GY, Herzenberg AM, Kassiri Z, Wong D, Reich H, Khokha R, et al. Loss of angiotensin-converting enzyme-2 leads to the late development of angiotensin II-dependent glomerulosclerosis. Am J Pathol. 2006; 168:1808–1820. PMID: 16723697.

33. Prieto-Carrasquero MC, Harrison-Bernard LM, Kobori H, Ozawa Y, Hering-Smith KS, Hamm LL, et al. Enhancement of collecting duct renin in angiotensin II-dependent hypertensive rats. Hypertension. 2004; 44:223–229. PMID: 15226276.

34. Prieto-Carrasquero MC, Kobori H, Ozawa Y, Gutiérrez A, Seth D, Navar LG. AT1 receptor-mediated enhancement of collecting duct renin in angiotensin II-dependent hypertensive rats. Am J Physiol Renal Physiol. 2005; 289:F632–F637. PMID: 15870381.

35. Kobori H, Prieto-Carrasquero MC, Ozawa Y, Navar LG. AT1 receptor mediated augmentation of intrarenal angiotensinogen in angiotensin II-dependent hypertension. Hyperension. 2004; 43:1126–1132.

36. Lavoie JL, Lake-Bruse KD, Sigmund CD. Increased blood pressure in transgenic mice expressing both human renin and angiotensinogen in the renal proximal tubule. Am J Physiol Renal Physiol. 2004; 286:F965–F971. PMID: 15075192.

37. Kobori H, Ozawa Y, Suzaki Y, Nishiyama A. Enhanced intrarenal angiotensinogen contributes to early renal injury in spontaneously hypertensive rats. J Am Soc Nephrol. 2005; 16:2073–2080. PMID: 15888567.

38. Kobori H, Nishiyama A, Abe Y, Navar LG. Enhancement of intrarenal angiotensinogen in Dahl salt-sensitive rats on high salt diet. Hypertension. 2003; 41:592–597. PMID: 12623964.

39. Singh R, Singh AK, Leehey DJ. A novel mechanism for angiotensin II formation in streptozotocin-diabetic rat glomeruli. Am J Physiol Renal Physiol. 2005; 288:F1183–F1190. PMID: 15701818.

40. Admiraal PJ, Derkx FH, Danser AH, Pieterman H, Schalekamp MA. Intrarenal de novo production of angiotensin I in subjects with renal artery stenosis. Hypertension. 1990; 16:555–563. PMID: 2228156.

41. Lai KN, Leung JC, Lai KB, To WY, Yeung VT, Lai FM. Gene expression of the renin-angiotensin system in human kidney. J Hypertens. 1998; 16:91–102. PMID: 9533422.

42. Mezzano S, Droguett A, Burgos ME, Ardiles LG, Flores CA, Aros CA, et al. Renin-angiotensin system activation and interstitial inflammation in human diabetic nephropathy. Kidney Int. 2003; 64(Suppl 86):S64–S70.

43. Miyake-Ogawa C, Miyazaki M, Abe K, Harada T, Ozono Y, Sakai H, et al. Tissue-specific expression of reninangiotensin system components in IgA nephropathy. Am J Nephrol. 2005; 25:1–12. PMID: 15644622.

44. Loghman-Adham M, Soto CE, Inagami T, Cassis L. The intrarenal renin-angiotensin system in autosomal dominant polycystic kidney disease. Am J Physiol Renal Physiol. 2004; 287:F775–F788. PMID: 15187005.

45. McPherson EA, Luo Z, Brown RA, LeBard LS, Corless CC, Speth RC, et al. Chymase-like angiotensin II-generating activity in end-stage human autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2004; 15:493–500. PMID: 14747398.