medigraphic.com
SPANISH

Medicina Interna de México

Colegio de Medicina Interna de México.
  • Contents
  • View Archive
  • Information
    • General Information        
    • Directory
  • Publish
    • Instructions for authors        
  • medigraphic.com
    • Home
    • Journals index            
    • Register / Login
  • Mi perfil

2012, Number 3

<< Back Next >>

Med Int Mex 2012; 28 (3)

Effect of trandolapril and its fixed-dose combination with verapamil on the levels of biopterins in hypertensive diabetic patients

Duran-Salgado MB, Vargas-Robles H, Del Valle-Mondragón L, Escalante-Acosta BA, Rubio-Guerra AF
Full text How to cite this article

Language: Spanish
References: 15
Page: 244-248
PDF size: 361.48 Kb.


Key words:

Tetrahydrobiopterin, Dihydrobiopterin, Trandolapril, Verapamil, Hypertensive diabetic patients.

ABSTRACT

Tetrahydrobiopterin (BH4) plays an essential role in regulating nitric oxide (NO) synthesis. When BH4 oxidized to dihydrobiopterin (BH2), leads to endothelial dysfunction and atherosclerosis. Recent studies show that BH4/BH2 ratio may be even more important than absolute BH4 for an adequate endothelial function. Both calcium channel blockers (CCB) and angiotensin converting enzyme inhibitors (ACEI) have shown to improve endothelial function. The aim of this study was to evaluate the effect of trandolapril (T) and its fixed-dose combination with verapamilo (TV) on biopterin levels and in BH4/BH2 ratio in hypertensive type-2 diabetic patients.
Material and Methods: Forty type-2 diabetic patients with never-treated hypertension were randomly assigned to two groups. One group received TV 2/180 mg once a day; the other group received T 2 mg once a day. Medication time in both groups: 3 months. BH4 and BH2 were measured by reverse phase high performance liquid chromatography with fluorescence detection at the beginning and end of the study. Patients were evaluated monthly for blood pressure, fasting serum glucose and adverse events. Statistical analysis was performed with the Shapiro-Wilk and Wilcoxon test.
Results: All patients experienced a significant reduction of blood pressure. Both therapeutics regimens increased the levels of BH4 (TV 3.85 to 9.95, T 5.23 to 10.13) and decreased the levels of BH2 (TV 9.94 to 6.87, T 8.36 to 7.47), and improved the BH4/BH2 ratio (TV 0.39 to 1.45, T 0.63 to 1.35) However TV produces a significantly greater increase in the BH4 levels (p ‹ 0.05) and in the BH4/BH2 ratio (p ‹ 0.01) when compared with monotherapy. No patient suffered adverse events.
Conclusion: Our results shown that a fixed dose of TV has more beneficial effects on biopterin parameters than monotherapy. This may explain the beneficial effects seen with combinations that included a CCB with an ACEI in high risk hypertensive patients.


REFERENCES

  1. Rubio AF. Vargas H. Maceda A. Vargas G. Rodriguez L. Escalante BA. Correlation between the levels of circulating adhesion molecules and atherosclerosis in hypertensive type-2 diabetic patients. Clin and Experiment Hypertens 2010;32:308-310.

  2. Rubio-Guerra AF. Vargas-Robles H. Ramos-Brizuela LM. Escalante-Acosta BA. Is tetrahydrobiopterin a therapeutic option in diabetic hypertensive patients? Integr Blood Press Contr 2010;3:125-132.

  3. Vasquez-Vivar J, Kalyanaraman B, Martasek P. Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc Natl Acad Sci U S A 1998;95:9220–9225.

  4. Takeda M. Yamashita T. Shinohara M. Sasaki N. Takaya T. Nakajima K y cols. Plasma tetrahydrobiopterin/dihydrobiopterin ratio. A posible marker of endothelial dysfunction. Cir J 2009;955-962.

  5. The Seven report of the Joint National Committee on Detection, Evaluation, and Treatment of high blood pressure. JNC 7. Complete version. Hypertension 2003;42:1206-1252.

  6. Programa de Salud del Adulto y del Anciano del Centro Nacional de Programas Preventivos y Control de Enfermedades de la Secretaría de Salud. Guía de Tratamiento Farmacológico y Control de la Hipertensión Arterial Sistémica. Rev Mex Cardiol 2011;22:1A-21A.

  7. Antoniades C, Bakogiannis C, Leeson P, Guzik TJ, Zhang MH, Tousoulis D. Rapid, direct effects of statin treatment on arterial redox state and nitric oxide bioavailability in human atherosclerosis via tetrahydrobiopterin-mediated endothelial nitric oxide synthase coupling. Circulation 2011;124:335-345.

  8. Rubio-Guerra AF, Vargas-Robles H. Vargas-Ayala G. Rodríguez- Lopez L. Escalante-Acosta BA. The effect of trandolapril and its fixed-dose combination with verapamil on circulating adhesion molecules levels in hypertensive patients with type 2 diabetes. Clin Exp Hypertens 2008;30:682-688.

  9. Heitzer T, Krohn K, Albers S, Meinertz T. Tetrahydrobiopterin improves endothelial vasodilation by increasing nitric oxide activity in patients with Type II diabetes mellitus. Diabetologia 2000;43:1435–1438.

  10. Vásquez-Vivar J. Tetrahydrobiopterin, Superoxide and Vascular Dysfunction. Free Radic Biol Med 2009;15(47):1108–1119.

  11. Förstermann U. Münzel T. Endothelial nitric oxide synthase in vascular disease. From marvel to menace. Circulation 2006;113:1708-1714.

  12. Schmidt TS. McNeill E. Douglas G. Crabtree MJ. Hale AB. Khoo J. y cols. Tetrahydrobiopterin supplementation reduces atherosclerosis and vascular inflammation in apolipoproteína E-knockout mice. Clinical Science 2010;119:131-142.

  13. Bakris GL. Sarafidis PA. Weir MR. Dahlöf B. Pitt B. Jamerson K. Velazquez EJ. Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial. Lancet 2010;375:1173-1181.

  14. Jamerson K, Weber MA, Bakris GL, Dahlof B, Pitt B, Shi V, Hester A, Gupte J, Gatlin M, Velazquez EJ. Benazepril plus Amlodipine or Hydrochlorothiazide for Hypertension in High-Risk Patients. N Engl J Med 2008;359:2417-2428.

  15. Rubio AF, Arceo A. Lozano JJ, Vargas G. Rodríguez L. Ramos LM. Efficacy of a fixed-dose combination of trandolapril- verapamil in patients with stage-2 hypertension inadequately controlled by monotherapy. Clin Drug Invest 2005;25:445-451.




2020     |     www.medigraphic.com

Mi perfil

C?MO CITAR (Vancouver)

Med Int Mex. 2012;28