Skip to main content
SpringerLink
Log in

Angiotensin 2 type 1 receptor blockade different affects postishemic kidney injury in normotensive and hypertensive rats

  • Mini Review
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

Many studies demonstrated that angiotensin 2 type 1 receptor (AT1R) blockade accelerates renal recovery in post-ischaemic kidney but there are many controversies related to its net effect on kidney structure and function. During the past years, our research group was trying to define the pathophysiological significance of the renin–angiotensin system on post-ischemic acute renal failure (ARF) development in normotensive Wistar as well as hypertensive rats (SHR). This review mostly summarizes our experience in that field. Our previous studies in normotensive rats revealed that AT1R blockade, except slightly renal vascular resistance improvement, had no other obvious beneficial effects, and therefore implies angiotensin 2 (Ang-2) overexpression as non-dominant on kidney reperfusion injuries development. Similarly it was observed in Wistar rats with induced mild (L-NAME, 3 mg/kg b.w.) nitric oxide (NO) deficiency. Expectably, in strong induced (L-NAME, 10 mg/kg b.w.) NO deficiency associated with ARF, massive tubular injuries indicate harmful effects of AT1R blockade, implying strongly disturbed glomerular filtration and suggesting special precaution related to AT1R blockers usage. Opposite to previous, by our opinion, AT1R antagonism promises new advance in treatment of essentially hypertensive subjects who develop ARF. Increased glomerular filtration, diminished oxidative stress, and most importantly improved tubular structure in postishemic SHR treated with AT1R blocker losartan, implicate Ang-2 over production as potently agent in the kidney ischemic injury, partly trough generation of reactive oxygen species. These data contribute understanding the pathogenesis of this devastating illness in hypertensive surroundings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Barroso LC, Silveira KD, Lima CX, Borges V, Bader M, Rachid M, et al. (2012) Renoprotective effects of AVE0991, a nonpeptide mas receptor agonist, in experimental acute renal injury. Int J Hypertens 2012:808726. doi:10.1155/2012/808726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bedford M, Farmer CKT, Irving J, Stevens PE (2015) Acute kidney injury: an acceptable risk of treatment with renin-angiotensin system blockade in primary care? Canadian Journal of Kidney Health and Disease 2:14. doi:10.1186/s40697-015-0044-y

    Article  PubMed  PubMed Central  Google Scholar 

  3. Berry C, Touyz R, Dominiczak AF, Webb RC, Johns DG (2001) Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide. Am J Phys 281:H2337–H2365

    CAS  Google Scholar 

  4. Bolterman RJ, Manriquez MC, Ortiz Ruiz MC, Juncos LA, Romero JC (2005) Effects of captopril on the renin angiotensin system, oxidative stress, and endothelin in normal and hypertensive rats. Hypertension 46:943–947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Carey RM, Siragy HM (2003) Newly recognized components of the renin-angiotensin system: potential roles in cardiovascular and renal disease. Endocr Rev 24:261–271

    Article  CAS  PubMed  Google Scholar 

  6. Carey RM (2005) Cardiovascular and renal regulation by the angiotensin type 2 receptor: the AT2 receptor comes of age. Hypertension 45:840–844

    Article  CAS  PubMed  Google Scholar 

  7. Crowley SD, Gurley SB, Herrera MJ, Ruiz P, Griffiths R, et al. (2006) Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proc Natl Acad Sci U S A 103:17985–17990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. de Gasparo M, Catt KJ, Inagami T, Wright JW, Unger T (2000) International union of pharmacology. XXIII. The angiotensin II receptors. Pharmacol Rev 52:415–472

    PubMed  Google Scholar 

  9. Fang F, Liu GC, Zhou X, Yang S, Reich HN, et al. (2013) Loss of ACE2 exacerbates murine renal ischemia-reperfusion injury. PLoS One 8:e71433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ferrario CM (2011) ACE2: more of Ang-(1–7) or less Ang II? Curr Opin Nephrol Hypertens 20:1–6

    Article  CAS  PubMed  Google Scholar 

  11. Finn WF (1980) Enhanced recovery from postischemic acute renal failure. Micropuncture studies in the rat. Circ Res 46:440–448

    Article  CAS  PubMed  Google Scholar 

  12. Gobe G, Zhang XJ, Willgoss DA, Schoch E, Hogg NA, et al. (2000) Relationship between expression of Bcl-2 genes and growth factors in ischemic acute renal failure in the rat. J Am Soc Nephrol 11:454–467

    CAS  PubMed  Google Scholar 

  13. Hashimoto N, Maeshima Y, Satoh M, Odawara M, Sugiyama H, Kashihara N, Matsubara H, Yamasaki Y, Makino H (2004) Overexpression of angiotensin type 2 receptor ameliorates glomerular injury in a mouse remnant kidney model. Am J Physiol Renal Physiol 286:F516–F525

    Article  CAS  PubMed  Google Scholar 

  14. Heeba GH (2011) Angiotensin II receptor blocker, losartan, ameliorates gentamicin-induced oxidative stress and nephrotoxicity in rats. Pharmacology 87:232–240

    Article  CAS  PubMed  Google Scholar 

  15. Honda N, Hishida A (1993) Pathophysiology of experimental nonoliguric acute renal failure. Kidney Int 43:513–521

    Article  CAS  PubMed  Google Scholar 

  16. Inal M, Altinisik M, Bilgin MD (2002) The effect of quercetin on renal ischemia and reperfusion injury in the rat. Cell Biochem Funct 20:291–296

    Article  CAS  PubMed  Google Scholar 

  17. Ishikawa I, Harris RC (1991) Angiotensin actions in the kidney: renewed insights into the old hormone. Kidney Int 4:583–596

    Article  Google Scholar 

  18. Ivanov M, Mihailović-Stanojević N, Grujić Milanović J, Jovović Đ, Marković-Lipkovski J, Ćirović S, Miloradović Z (2014) Losartan improved antioxidant defense, renal function and structure of postischemic hypertensive kidney. PLoS One. doi:10.1371/journal.pone.0096353

    Google Scholar 

  19. Ivanov M, Mihailović-Stanojević N, Grujić Milanović J, Jovović Đ, Miloradović Z (2011) Prevention of systemic and regional haemodynamic alterations, hypercreatininemia, hyperuremia and hyperphosphatemia by losartan in hypertension with acute renal failure. Acta Physiol Hung 98:1–7

    Article  CAS  PubMed  Google Scholar 

  20. Iwai M, Horiuchi M (2009) Devil and angel in the renin–angiotensin system: ACE–angiotensin II–AT1 receptor axis vs. ACE2–angiotensin-(1–7)–mas receptor axis. Hypertens Res 32:533–536

    Article  CAS  PubMed  Google Scholar 

  21. Jerkić M, Miloradović Z, Jovović D, Mihailović-Stanojević N, Elena JV, Nastić-Mirić D, Grujić-Adanja G, Rodriguez-Barbero A, Marković-Lipkovski J, Vojvodić SB, Manero MV, Prieto MP, Lopez-Novoa JM (2004) Relative roles of endothelin-1 and angiotensin II in experimental post-ischaemic acute renal failure. Nephrol Dial Transplant 19:83–94

    Article  CAS  PubMed  Google Scholar 

  22. Jerkić M, Varagić J, Jovović Đ, Radujković-Kuburović G, Nastić-Mirić D, Adanja-Grujić G, Marković-Lipkovski J, Dimitrijević J, Miloradović Z, Vojvodić SB (1999) L-arginine reduces tubular cell injury in acute postischemic renal failure. Nephrol Dial Transplant 14:1398–1407

    Article  PubMed  Google Scholar 

  23. Jones ES, Vinh A, McCarthy CA, Gaspari TA, Widdop RE (2008) AT2 receptors: functional relevance in cardiovascular disease. Pharmacol Ther 120:292–316

    Article  CAS  PubMed  Google Scholar 

  24. Kakoki M, Hirata Y, Hayakawa H, Suzuki E, Nagata D, Tojo A, Nishimatsu H, Nakanishi N, Hattori Y, Kikuchi K, Nagano T, Omata M (2000) Effects of tetrahydrobiopterin on endothelial dysfunction in rats with ischemic acute renal failure. J Am Soc Nephrol 11:301–309

    CAS  PubMed  Google Scholar 

  25. Kim SJ, Lim YT, Kim BS, et al. (2000) Mechanism of reduced GFR in rabbits with ischemic acute renal failure. Renal Fail 22:129–141

    Article  CAS  Google Scholar 

  26. Koh KK, Ahn JY, Han SH, Kim DS, Jin DK, et al. (2003) Pleiotropic effects of angiotensin II receptor blocker in hypertensive patients. J Am Coll Cardiol 42:905–910

    Article  CAS  PubMed  Google Scholar 

  27. Kontogiannis J, Burns KD (1998) Role of AT1 angiotensin II receptors in renal ischemic injury. Am J Phys 274:F79–F90

    CAS  Google Scholar 

  28. Matsumura Y, Nishiura M, Deguchi S, Hashimoto N, Ogawa T, Seo R (1998) Protective effect of FK409, a spontaneous nitric oxide releaser, on ischemic acute renal failure in rats. J Pharmacol ExpTher 287:1084–1091

    CAS  Google Scholar 

  29. Miller GJ, Miller NE (1975) Plasma-high-density-lipoprotein concentration and development of ischaemic heart-disease. Lancet 1:16–19

    Article  CAS  PubMed  Google Scholar 

  30. Miloradović Z, Jerkić M, Jovović Đ, Mihailović-Stanojević N, Grujić Milanović J, et al. (2007) Bosentan and losartan ameliorate acute renal failure associated with mild but not strong NO blockade. Nephrol Dial Transplant 22:2476–2484

    Article  CAS  PubMed  Google Scholar 

  31. Miyata N, Park F, Li XF, Cowley AW Jr (1999) Distribution of angiotensin AT1 and AT2 receptor subtypes in the rat kidney. Am J Physiol Renal Physiol 277:F437–F446

    CAS  Google Scholar 

  32. Navar LG, Harrison-Bernard LM, Wang CT, Cervenka L, Mitchell KD (1999) Concentrations and actions of intraluminal angiotensin II. J Am Soc Nephrol 10:S189–S195

    CAS  PubMed  Google Scholar 

  33. Ozono R, Wang Z-Q, Moore AF, Inagami T, Siragy HM, Carey RM (1997) Expression of the subtype 2 angiotensin (AT2) receptor protein in rat kidney. Hypertension 30:1238–1246

    Article  CAS  PubMed  Google Scholar 

  34. Padia SH, Carey RM (2013) AT2 receptors: beneficial counter-regulatory role in cardiovascular and renal function. Pflugers Arch 465:99–110

    Article  CAS  PubMed  Google Scholar 

  35. Rajagopalan S, Kurz S, Munzel T, Tarpey M, Freeman BA, et al. (1996) Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 97:1916–1923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ritz E, Haxsen V (2003) Angiotensin II and oxidative stress: an unholy alliance. J Am Soc Nephrol 14:2985–2987

    Article  PubMed  Google Scholar 

  37. Silici S, Ekmekcioglu O, Kanbur M, Deniz K (2011) The protective effect of royal jelly against cisplatin-induced renal oxidative stress in rats. World J Urol 29:127–132

    Article  PubMed  Google Scholar 

  38. Stein HJ, Lifschitz DM, Barnes BL (1978) Current concepts on the pathophysiology of acute renal failure. Am J Phys 234:F171–F181

    CAS  Google Scholar 

  39. Therrien F, Lemieux P, Belanger S, Agharazii M, Lebel M, et al. (2009) Protective effects of angiotensin AT1 receptor blockade in malignant hypertension in the rat. Eur J Pharmacol 607:126–134

    Article  CAS  PubMed  Google Scholar 

  40. Thiemermann C, Patel NS, Kvale EO, Cockerill GW, Brown PA, et al. (2003) High density lipoprotein (HDL) reduces renal ischemia/reperfusion injury. J Am Soc Nephrol 14:1833–1843

    Article  CAS  PubMed  Google Scholar 

  41. Tikellis C, Bernardi S, Burns WC (2011) Angiotensin converting enzyme 2 is a key modulator of the renin–angiotensin system in cardiovascular and renal disease. Curr Opin Nephrol Hypertens 20:62–68

    Article  CAS  PubMed  Google Scholar 

  42. Vazquez E, Coronel I, Bautista R, Romo E, Villalon CM, Avila-Casado MC, Soto V, Escalante B (2005) Angiotensin II-dependent induction of AT(2) receptor expression after renal ablation. Am J Physiol Renal Physiol 288:F207–F213

    Article  CAS  PubMed  Google Scholar 

  43. Wang Z, Liu Y, Han Y, Guan W, Kou X, Fu J, et al. (2013) Protective effects of aliskiren on ischemia–reperfusion-induced renal injury in rats. Eur J Pharmacol 718:160–166

    Article  CAS  PubMed  Google Scholar 

  44. Wolf G, Wenzel U, Jablonski K, Brundert M, Rinninger F (2005) Angiotensin II down-regulates the SR-BI HDL receptor in proximal tubular cells. Nephrol Dial Transplant 20:1222–1227

    Article  CAS  PubMed  Google Scholar 

  45. Zafari AM, Ushio-Fukai M, Akers M, Yin Q, Shah A, et al. (1998) Role of NADH/NADPH oxidase-derived H2O2 in angiotensin II-induced vascular hypertrophy. Hypertension 32:488–495

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant (projects OI175096) from the Ministry of Education, Science and Technological Development of Serbia.

Author information

Authors and Affiliations

  1. Institute for Medical Research University of Belgrade, Dr Subotića 4, PO Box 102, Belgrade, 11129, Serbia

    Zoran Miloradović, Milan Ivanov, Đurđica Jovović, Danijela Karanović, Una Jovana Vajić, Nevena Mihailović-Stanojević & Jelica Grujić Milanović

  2. Institute of Pathology, Medical School University of Belgrade, Belgrade, Serbia

    Jasmina Marković-Lipkovski

Authors
  1. Zoran Miloradović
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Milan Ivanov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Đurđica Jovović
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Danijela Karanović
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Una Jovana Vajić
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jasmina Marković-Lipkovski
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nevena Mihailović-Stanojević
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jelica Grujić Milanović
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zoran Miloradović.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Miloradović, Z., Ivanov, M., Jovović, Đ. et al. Angiotensin 2 type 1 receptor blockade different affects postishemic kidney injury in normotensive and hypertensive rats. J Physiol Biochem 72, 813–820 (2016). https://doi.org/10.1007/s13105-016-0514-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-016-0514-4

Keywords

Search

Navigation