Skip to main content
Log in

Effects of Olmesartan Medoxomil an Angiotensin II Type 1 Receptor Antagonist, on Plasma Concentration of B-Type Natriuretic Peptide, in Hypertensive Patients with Type 2 Diabetes Mellitus

A Preliminary, Observational, Open-Label Study

  • Original Research Article
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Background and Objective: Angiotensin II type 1 (AT1) receptor antagonists (angiotensin receptor blockers [ARBs]) are widely used for the treatment of not only hypertension but also cardiac dysfunction. B-type natriuretic peptide (BNP) is secreted mainly by the cardiac ventricle and plays an important role in the regulation of blood pressure (BP) and body fluid. It has been established that the plasma level of BNP is increased in patients with chronic heart failure in proportion to the severity of cardiac dysfunction. Because cardiac dysfunction is closely associated with a high risk of mortality in patients with diabetes mellitus, early identification and prevention of cardiac dysfunction are important. The objective of this study was to determine the effects of olmesartan medoxomil, a novel ARB, on the plasma level of BNP in hypertensive patients with type 2 diabetes.

Methods: This was a preliminary, prospective, observational, open-label study. Sixty-eight type 2 diabetic patients with hypertension (systolic BP [SBP] ≥140 mmHg or diastolic BP [DBP] ≥90 mmHg) received olmesartan medoxomil 10–20 mg/day for 24 weeks. Plasma levels of BNP, as well as several clinical parameters of glycaemic control and lipid metabolism, were compared before and after 24 weeks of treatment. Another group consisting of 22 age-and body mass index-matched subjects not treated with olmesartan medoxomil was observed for reference purposes.

Results: In the olmesartan medoxomil group, mean ± SD SBP decreased from 152.8 ± 16.4 at baseline to 146.8 ± 14.4mmHg after 24 weeks’ treatment (p < 0.05); similarly, mean ± SD DBP decreased from 85.6 ± 10.5 to 81.3 ± 11.6 mmHg (p < 0.05). In 53 subjects in whom plasma levels of BNP could be measured both before and after treatment, mean ± SD BNP decreased from 41.3 ± 49.9 to 32.5 ± 36.3 pg/mL (p < 0.05). Change in plasma BNP level over the 24-week treatment period in the olmesartan medoxomil group was not correlated with change in SBP or DBP. Multiple regression analysis revealed that change in plasma BNP level was not correlated with baseline value of or change in any other parameters. No other parameters in the olmesartan medoxomil group, and no parameters in the non-olmesartan medoxomil reference group, showed significant changes.

Conclusion: The current preliminary study showed that olmesartan medoxomil treatment might decrease plasma BNP levels, independent of its BP-lowering effect, in hypertensive patients with type 2 diabetes.

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

Access this article

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

Instant access to the full article PDF.

Table I
Table II
Fig. 1
Table III
Table IV

Similar content being viewed by others

References

  1. King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care 1998; 21: 1414–31

    Article  PubMed  CAS  Google Scholar 

  2. Yoon KH, Lee JH, Kim JW, et al. Epidemic obesity and type 2 diabetes in Asia. Lancet 2006; 368: 1681–8

    Article  PubMed  Google Scholar 

  3. Nakao K, Ogawa Y, Suga S, et al. Molecular biology and biochemistry of the natriuretic peptide system: I. Natriuretic peptides. J Hypertens 1992; 10: 907–12

    PubMed  CAS  Google Scholar 

  4. Wilkins MR, Redondo J, Brown LA. The natriuretic-peptide family. Lancet 1997; 349: 1307–10

    Article  PubMed  CAS  Google Scholar 

  5. Yasue H, Yoshimura M, Sumida H, et al. Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation 1994; 90: 195–203

    Article  PubMed  CAS  Google Scholar 

  6. Tsutamoto T, Wada A, Maeda K, et al. Attenuation of compensation of endogenous cardiac natriuretic peptide system in chronic heart failure: prognostic role of plasma brain natriuretic peptide concentration in patients with chronic symptomatic left ventricular dysfunction. Circulation 1997; 96: 509–16

    Article  PubMed  CAS  Google Scholar 

  7. Kadowaki T, Iwamoto Y, Sekihara H, et al. Clinical use of plasma BNP concentrations for diabetic patient. J Jpn Diab Soc 2001; 44: 927–33

    Google Scholar 

  8. Igarashi M, Jimbu Y, Hirata A, et al. Characterization of plasma brain natriuretic peptide level in patients with type 2 diabetes. Endocr J 2005; 52: 353–62

    Article  PubMed  CAS  Google Scholar 

  9. Anan F, Takahashi N, Ooie T, et al. Candesartan, an angiotensin II receptor blocker, improves left ventricular hypertrophy and insulin resistance. Metabolism 2004; 53: 777–81

    Article  PubMed  CAS  Google Scholar 

  10. Kasama S, Toyama T, Kumakura H, et al. Effects of candesartan on cardiac sympathetic nerve activity in patients with congestive heart failure and preserved left ventricular ejection fraction. J Am Coll Cardiol 2005; 45: 661–7

    Article  PubMed  CAS  Google Scholar 

  11. Kasama S, Toyama T, Hatori T, et al. Comparative effects of valsartan and enalapril on cardiac sympathetic nerve activity and plasma brain natriuretic peptide in patients with congestive heart failure. Heart 2006; 92: 625–30

    Article  PubMed  CAS  Google Scholar 

  12. Symeonides P, Koulouris S, Vratsista E, et al. Both ramipril and telmisartan reverse indices of early diabetic cardiomyopathy: a comparative study. Eur J Echocardiogr 2007; 8: 480–6

    Article  PubMed  Google Scholar 

  13. Van den Meiracker AH, Lameris TW, Van de Ven LL, et al. Increased plasma concentration of natriuretic peptides by selective β1-blocker bisoprolol. J Cardiovasc Pharmacol 2003; 42: 462–8

    Article  PubMed  Google Scholar 

  14. Miura S, Fujino M, Hanzawa H, et al. Molecular mechanism underlying inverse agonist of angiotensin II type 1 receptor. J Biol Chem 2006; 281: 19288–95

    Article  PubMed  CAS  Google Scholar 

  15. Miura S, Kiya Y, Kanazawa T, et al. Differential bonding interactions of inverse agonists of angiotensin II type 1 receptor in stabilizing the inactive state. Mol Endocrinol 2008; 22: 139–46

    Article  PubMed  CAS  Google Scholar 

  16. Yano Y, Katsuki A, Gabazza EC, et al. Plasma brain natriuretic peptide levels in normotensive noninsulin-dependent diabetic patients with microalbuminuria. J Clin Endocrinol Metab 1999; 84: 2353–6

    Article  PubMed  CAS  Google Scholar 

  17. Ogawa Y, Nakao K, Mukoyama M, et al. Natriuretic peptides as cardiac hormones in normotensive and spontaneously hypertensive rat: the ventricle is a major site of synthesis and secretion of brain natriuretic peptide. Circ Res 1991; 69: 491–500

    Article  PubMed  CAS  Google Scholar 

  18. Magga J, Marttila M, Mantymaa P, et al. Brain natriuretic peptide in plasma, atria, and ventricles of vasopressin- and phenylephrine-infused conscious rat. Endocrinology 1994; 134: 2505–15

    Article  PubMed  CAS  Google Scholar 

  19. Nakamoto T, Harasawa H, Akimoto K, et al. Effects of olmesartan medoxomil as an angiotensin II-receptor blocker in chronic hypoxic rats. Eur J Pharmacol 2005; 528: 43–51

    Article  PubMed  CAS  Google Scholar 

  20. Ogawa T, Veinot JP, Kuroski de Bold ML, et al. Angiotensin II receptor antagonism reverts the selective cardiac BNP upregulation and secretion observed in myocarditis. Am J Physiol Heart Circ Physiol 2008; 294: 2596–603

    Article  Google Scholar 

  21. Oparil S, Williams D, Chrysant SG, et al. Comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the control of essential hypertension. J Clin Hypertens 2001; 3: 283–91

    Article  CAS  Google Scholar 

  22. Julius S, Nesbitt SD, Egan BM, et al., TRial Of Preventing HYpertension (TROPHY) study investigators. Feasibility of treating prehypertension with an angiotensin-receptor blocker. N Engl J Med 2006; 354: 1685–97

    Article  PubMed  CAS  Google Scholar 

  23. Cappuccio FP, Markandu ND, Sagnella GA, et al. Effects of amlodipine on urinary sodium excretion, renin-angiotensin-aldosterone system, atrial natriuretic peptide and blood pressure in essential hypertension. J Hum Hypertens 1991; 5: 115–9

    PubMed  CAS  Google Scholar 

  24. Lambers Heerspink HJ, Brinkman JW, Bakker SJ, et al. Update on microalbuminuria as a biomarker in renal and cardiovascular disease. Curr Opin Nephrol Hypertens 2006; 15: 631–6

    Article  Google Scholar 

  25. Ma TKW, Kam KKH, Yan BP, et al. Renin-angiotensin-aldosterone system blockade for cardiovascular disease: current status. Br J Pharmacol 2010; 160: 1273–92

    Article  PubMed  CAS  Google Scholar 

  26. Haller H, Viberti GC, Mimran A, et al. Preventing microalbuminuria in patients with diabetes: rationale and design of the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study. J Hypertens 2006; 24: 403–8

    Article  PubMed  CAS  Google Scholar 

  27. Ritz E, Viberti GC, Ruilope LM, et al. Determinants of urinary albumin excretion within the normal range in patients with type 2 diabetes: the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study. Diabetologia 2010; 53: 49–57

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr Wendy Gray for editing the manuscript. No sources of funding were used to assist in the conduct of this study or the preparation of the manuscript. The authors have no conflicts of interest that are directly relevant to the content of this study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Toshihide Kawai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kawai, T., Takei, I., Shimada, A. et al. Effects of Olmesartan Medoxomil an Angiotensin II Type 1 Receptor Antagonist, on Plasma Concentration of B-Type Natriuretic Peptide, in Hypertensive Patients with Type 2 Diabetes Mellitus. Clin. Drug Investig. 31, 237–245 (2011). https://doi.org/10.2165/11586510-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11586510-000000000-00000

Keywords

Navigation