Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Distinct time courses of renal protective action of angiotensin receptor antagonists and ACE inhibitors in chronic renal disease

Journal of Human Hypertension volume 17, pages 271–276 (2003)Cite this article

Abstract

Although the angiotensin receptor antagonist (ARB) shares the angiotensin-II-blocking activity with the angiotensin-converting enzyme inhibitor (ACE-I), pharmacological mechanisms of action of these agents differ. We evaluated the temporal profiles of action of ACE-I and ARB on urinary protein excretion and nitrate/nitrate (NOx) excretion in hypertensive (140 and/or 90 mmHg) patients with chronic renal disease (serum creatinine<265 (range, 44–265) μmol/l or creatinine clearance>30 (range, 30–121) ml/min). Patients with mild (<1 g/day; range, 0.4–1.0) and moderate proteinuria (>1 g/day; range, 1.1–6.9) were randomly assigned to ACE-I- and ARB-treated groups, and were treated with ACE-I (trandolapril or perindopril) or ARB(losartan or candesartan) for 48 weeks. In all groups, treatment with ACE-I or ARB decreased blood pressure to the same level, but had no effect on creatinine clearance. In patients with mild proteinuria, neither ACE-I nor ARB altered urinary protein excretion. In patients with moderate proteinuria, ACE-I caused 44±6% reduction in proteinuria (from 2.7±0.5 to 1.5±0.4 g/day, n=14) at 12 weeks, and this beneficial effect persisted throughout the protocol (48 weeks, 1.2±0.2 g/day). In contrast, ARB did not produce a significant decrease in proteinuria at 12 weeks (23±8%, n=13), but a 41±6% reduction in proteinuria was observed at 48 weeks. Similarly, although early (12 weeks) increases in urinary NOx excretion were observed with ACE-I (from 257±70 to 1111±160 μmol/day) and ARB (from 280±82 to 723±86 μmol/day), the ARB-induced increase in NOx excretion was smaller than that by ACE-I (P<0.05). In conclusion, although both ACE-I and ARB reduce blood pressure similarly, the effect of these agents on proteinuria differs in chronic renal disease with moderate proteinuria. Relatively early onset of the proteinuria-reducing effect was observed with ACE-I, which paralleled the increase in urinary NOx excretion. Conversely, ARB decreased proteinuria and increased urinary NOx excretion gradually. These time course-dependent changes in proteinuria and urinary NOx may reflect the pharmacological property of ACE-I and ARB, with regard to the action on bradykinin.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Anderson S, Rennke HG, Brenner BM . Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat. J Chin Invest 1986; 77: 1993–2000.

    Article  CAS  Google Scholar 

  2. Taguma Y et al. Effect of captopril on heavy proteinuria in azotemic diabetics. N Engl J Med 1985; 313: 1617–1620.

    Article  CAS  Google Scholar 

  3. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD . The effect of angiotensin-converting enzyme inhibition on diabetic nephropathy. N Engl J Med 1993; 326: 1456–1462.

    Article  Google Scholar 

  4. Maschio G et al. AIPRI Study Group. effect of the angiotensin-converting enzyme inhibitor benazepril on the progression of chronic renal insufficiency. N Engl J Med 1996; 334: 939–945.

    Article  CAS  Google Scholar 

  5. Brenner BM et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861–869.

    Article  CAS  Google Scholar 

  6. Lewis EJ et al. Collaborative Study Group. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851–860.

    Article  CAS  Google Scholar 

  7. Kon V, Fogo A, Ichikawa I . Bradykinin causes selective efferent arteriolar dilation during angiotensin I converting enzyme inhibition. Kidney Int 1993; 44: 545–550.

    Article  CAS  Google Scholar 

  8. Matsuda H et al. Zonal heterogeneity in action of angiotensin-converting enzyme inhibitor on renal microcirculation: role of intrarenal bradykinin. J Am Soc Nephrol 1999; 10: 2272–2282.

    CAS  PubMed  Google Scholar 

  9. Gainer JV et al. Effect of bradykinin-receptor blockade on the response to angiotensin-converting-enzyme inhibitor in normotensive and hypertensive subjects. N Engl J Med 1998; 339: 1285–1292.

    Article  CAS  Google Scholar 

  10. Siragy HM, Jaffa AA, Margolius HS, Carey RM: Renin–angiotensin system modulates renal bradykinin production. Am J Physiol 1996; 271: R1090–R1095.

    CAS  PubMed  Google Scholar 

  11. Nishimoto M et al. Significance of chymase-dependent angiotensin II-forming pathway in the development of vascular proliferation. Circulation 2001; 104: 1274–1279.

    Article  CAS  Google Scholar 

  12. Russo D et al. Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy. Am J Kidney Dis 2001; 38: 18–25.

    Article  CAS  Google Scholar 

  13. Tokuyama H et al. Role of intrarenal angiotensin II (AII) and cyclooxygenase (COX)-1/2 in chronic ischemic nephropathy. J Hypertens 2000; 18 (Suppl 4): S12.

    Google Scholar 

  14. Ohta K et al. A novel in vivo assay system for consecutive measurement of brain nitric oxide production combined with the microdialysis technique. Neurosci Lett 1994; 176: 165–168.

    Article  CAS  Google Scholar 

  15. Liu Y-H et al. Effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure. Role of kinins and angiotensin II type 2 receptors. J Clin Invest 1997; 99: 1926–1935.

    Article  CAS  Google Scholar 

  16. Carey RM, Jin X, Wang Z, Siragy HM . Nitric oxide: a physiological mediator of the type 2 (AT2) angiotensin receptor. Acta Physiol Scand 2000; 168: 65–71.

    Article  CAS  Google Scholar 

  17. Adler L et al. Angiotensin converting enzyme inhibitor therapy in children with Alport syndrome: effect on urinary albumin, TGF-B, and nitrite excretion. BMC Nephrol 2002; 3: 2.

    Article  Google Scholar 

  18. Rahma M et al. Effects of furosemide on the tubular reabsorption of nitrates in anesthetized dogs. Eur J Pharmacol 2001; 428: 113–119.

    Article  CAS  Google Scholar 

  19. Sosa-Canache B, Cierco M, Gutierrez CI, Israel A . Role of bradykinin and nitric oxide in the AT2 receptor-mediated hypotension. J Hum Hypertens 2000; 14: 4S40–4S46.

    Article  Google Scholar 

  20. Siragy HM, de Gasparo M, Carey RM . Angiotensin type 2 receptor mediates valsartan-induced hypotension in conscious rats. Hypertension 2000; 35: 1074–1077.

    Article  CAS  Google Scholar 

  21. Weir MR, Henrich WL . Theoretical basis and clinical evidence for differential effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor subtype 1 blockers. Curr Opin Nephrol Hypertens 2000; 9: 403–411.

    Article  CAS  Google Scholar 

  22. Ehara T, Shigematsu H . Contribution of mast cells to the tubulointerstitial lesions in IgA nephritis. Kidney Int 1998; 54: 1675–1683.

    Article  CAS  Google Scholar 

  23. Ghiadoni L et al. Effect of the angiotensin II type 1 receptor blocker candesartan on endothelial function in patients with essential hypertension. Hypertension 2000; 35 (1 Part 2): 501–506.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Ashikaga Red Cross Hospital, Honjo, Ashikaga, Tochigi, Japan

    H Matsuda

  2. Department of Internal Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan

    H Matsuda, K Hayashi & T Saruta

Authors
  1. H Matsuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Saruta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K Hayashi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Matsuda, H., Hayashi, K. & Saruta, T. Distinct time courses of renal protective action of angiotensin receptor antagonists and ACE inhibitors in chronic renal disease. J Hum Hypertens 17, 271–276 (2003). https://doi.org/10.1038/sj.jhh.1001543

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.jhh.1001543

Keywords

This article is cited by

Search

Advanced search

Quick links