2012, Number 3
Effect of trandolapril and its fixed-dose combination with verapamil on the levels of biopterins in hypertensive diabetic patients
Language: Spanish
References: 15
Page: 244-248
PDF size: 361.48 Kb.
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
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.
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.