-
[show abstract]
[hide abstract]
ABSTRACT: Endothelial dysfunction is a common feature in type-2 diabetic patients and is associated with inflammation, increased levels of circulating soluble adhesion molecules and atherosclerosis. Insufficiency of tetrahydrobiopterin leads to uncoupling of the nitric oxide synthase enzyme an endothelial dysfunction. The aim of this study: was to evaluate if there is a relationship between the levels of circulating soluble adhesion molecules and the levels of biopterins in normotensive type-2 diabetic patients. Methods: We studied 30 normotensive type-2 diabetic patients in whom VCAM-1, ICAM-1 and E-selectin were measured by ELISA. Additionally, Biopterins were measured by reverse phase high performance liquid chromatography with fluorescence detection. The levels of circulating adhesion molecules and biopterins were correlated using the Spearman correlation coefficient test. Statistical analysis was performed with ANOVA. Results: We did not find any relationship between absolute values of biopterins and soluble adhesion molecules. However, we observed significant inverse correlations between the BH4/BH2 ratio and VCAM-1 (r= -0.65, p < 0.001) with ICAM-1 (r= -0.69, p < 0.001) and with E-selectin (r=-0.64 p < 0.001), Conclusion: Our data suggest that systemic levels of adhesion molecules have an inverse association with the BH4/BH2 ratio in type 2 diabetic normotensive patients.
Endocrine, metabolic & immune disorders drug targets. 04/2012; 12(3):243-6.
-
[show abstract]
[hide abstract]
ABSTRACT: La tetrahidrobiopterina (BH4) es un cofactor esencial para la síntesis de óxido nítrico; la disminución de su síntesis o su oxidación a dihi-drobiopterina (BH2) provoca disfunción endotelial y aterosclerosis. Se ha postulado que el índice BH4/BH2 sea más importante que los valores de BH4 para mantener una adecuada función endotelial. Tanto los inhibidores de enzima convertidora como los calcioantagonistas han mostrado que mejoran la función endotelial. El objetivo de este estudio es evaluar el efecto del trandolaprilo (T) y su combinación a dosis fija con verapamilo (TV) en los niveles de biopterinas y en el índice BH4/BH2 en pacientes hipertensos con diabetes mellitus tipo 2. Material y método: cuarenta pacientes hipertensos con diabetes mellitus tipo 2, sin tratamiento antihipertensivo previo, fueron asigna-dos aleatoriamente a alguno de dos grupos de 20 pacientes. Un grupo recibió TV dosis 2/180 mg una vez al día y el otro grupo recibió T, dosis 2 mg diarios. En ambos grupos el tratamiento duró 3 meses. BH4 y BH2 se midieron por cromatografía líquida de fase reversa con fluorescencia al inicio y el final del estudio. Los pacientes fueron evaluados mensualmente y se registró presión arterial, glucemia de ayuno y efectos adversos. El análisis estadístico se realizó con las pruebas de Shapiro-Wilk y Wilcoxon. resultados: Todos los pacientes presentaron una reducción significativa de la presión arterial, los 2 regímenes terapéuticos aumentaron los niveles de BH4 (TV: 3.85 a 9.95; T: 5.23 a 10.13) y redujeron también los niveles de BH2 (TV: 9.94 a 6.87; T: 8.36 a 7.47) además de mejorar el índice BH4/BH2 (TV: 0.39 a 1.45; T: 0.63 a 1.35). Sin embargo, el incremento de BH4 con TV fue significativamente mayor (p < 0.05) que el observado con T. Lo mismo sucedió con el índice BH4/BH2 (p < 0.01). Ningún paciente presentó efectos adversos. Conclusión: Nuestros resultados muestran que dosis fija de TV brinda un beneficio mayor sobre los niveles de las biopterinas que la monoterapia. Esto explica, al menos en parte, los efectos favorables de las combinaciones que incluyen un calcioantagonista con un inhibidor de la enzima convertidora en pacientes hipertensos de alto riesgo cardiovascular. Palabras clave: tetrahidrobiopterina, dihidrobiopterina, trandolaprilo, verapamilo, pacientes hipertensos con diabetes tipo 2. 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.
Medicina Interna de Mexico 01/2012; 28(3):244.
-
[show abstract]
[hide abstract]
ABSTRACT: Alberto Francisco Rubio-Guerra1, Hilda Vargas-Robles2, Luz Maria Ramos-Brizuela1, Bruno Alfonso Escalante-Acosta21Metabolic Clinic, Hospital General de Ticomán SS DF, Mexico; 2Department of Molecular Biomedicine, Centro de Investigacion y de Estudios Avanzados del IPN, MexicoAbstract: Nitric oxide (NO) is an important regulator of vascular tone, and is also an antithrombotic, anti-inflammatory, antiproliferative, and antiatherogenic factor. Endothelial function is altered in patients with coronary artery disease, stroke, and peripheral artery disease, and endothelial dysfunction correlates with the risk factor profile for a patient. Hypertension and type 2 diabetes are risk factors for vascular disease, and are both pathologies characterized by loss of NO activity. Indeed, endothelial dysfunction is usually present in diabetic and/or hypertensive patients. Tetrahydrobiopterin is an essential cofactor for the NO synthase enzyme, and insufficiency of this cofactor leads to uncoupling of the enzyme, release of superoxide, endothelial dysfunction, progression of hypertension, and finally, proatherogenic effects. Tetrahydrobiopterin is also an important mediator of NO synthase regulation in type 2 diabetes and hypertension, and may be a rational therapeutic target to restore endothelial function and prevent vascular disease in these patients. The aim of this paper is to review the rationale for therapeutic strategies directed to biopterins as a target for vascular disease in type 2 diabetic hypertensive patients.Keywords: tetrahydrobiopterin, endothelial dysfunction, diabetes, hypertension, oxidative stress, nitric oxide, eNOS synthase uncoupling
Integrated Blood Pressure Control. 01/2010;
-
[show abstract]
[hide abstract]
ABSTRACT: Nitric oxide (NO) is an important regulator of vascular tone, and is also an antithrombotic, anti-inflammatory, antiproliferative, and antiatherogenic factor. Endothelial function is altered in patients with coronary artery disease, stroke, and peripheral artery disease, and endothelial dysfunction correlates with the risk factor profile for a patient. Hypertension and type 2 diabetes are risk factors for vascular disease, and are both pathologies characterized by loss of NO activity. Indeed, endothelial dysfunction is usually present in diabetic and/or hypertensive patients. Tetrahydrobiopterin is an essential cofactor for the NO synthase enzyme, and insufficiency of this cofactor leads to uncoupling of the enzyme, release of superoxide, endothelial dysfunction, progression of hypertension, and finally, proatherogenic effects. Tetrahydrobiopterin is also an important mediator of NO synthase regulation in type 2 diabetes and hypertension, and may be a rational therapeutic target to restore endothelial function and prevent vascular disease in these patients. The aim of this paper is to review the rationale for therapeutic strategies directed to biopterins as a target for vascular disease in type 2 diabetic hypertensive patients.
Integrated Blood Pressure Control 01/2010; 3:125-32.
-
[show abstract]
[hide abstract]
ABSTRACT: Endothelial dysfunction is a common feature in type-2 diabetic patients and in hypertension, and is associated with inflammation, increased levels of circulating soluble adhesion molecules, and atherosclerosis. The aim of this study was to evaluate the relationship between the levels of circulating soluble adhesion molecules and the degree of atherosclerosis in hypertensive type-2 diabetic patients. We studied 30 hypertensive type-2 diabetic patients in whom VCAM-1, ICAM-1, and E-selectin were measured by ELISA. Additionally, the intimal-medial thickness of both the common and internal carotid arteries was measured (B-mode ultrasound). The levels of circulating adhesion molecules and maximal carotid artery intimal-medial thicknesses were correlated using the Spearman correlation coefficient test. Statistical analysis was performed with ANOVA. We found significant correlations between ICAM-1 (r = 0.5) levels and maximal carotid artery intimal-medial thickness these patients. No correlation was observed with E-selectin and VCAM-1. Our results suggest that ICAM-1 is associated and correlated with the degree of atherosclerosis in type-2 diabetic hypertensive patients.
Clinical and Experimental Hypertension 01/2010; 32(5):308-10. · 1.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Endothelial dysfunction is a common feature in type-2 diabetic patients and is associated with inflammation, increased levels of circulating soluble adhesion molecules and atherosclerosis. The aim of this study was to evaluate the relationship between the levels of circulating soluble adhesion molecules and the degree of atherosclerosis in normotensive type-2 diabetic patients.
We found significant correlations between ICAM-1 (r = 0.69, p < 0.001 95% IC 0.65 to 0.82) and VCAM-1 (r = 0.4, p < 0.03, 95% IC 0.65 to 0.82) levels and maximal carotid artery intimal-medial thickness, whereas no correlation was observed with E-selectin.
We studied 30 normotensive type-2 diabetic patients in whom VCAM-1, ICAM-1 and E-selectin were measured by ELISA. Additionally, the intimal-medial thickness of both the common and internal carotid arteries was measured (B-mode ultrasound). The levels of circulating adhesion molecules and maximal carotid artery intimal-medial thicknesses were correlated using the Spearman correlation coefficient test. Statistical analysis was performed with ANOVA.
Our results suggest that ICAM-1 and VCAM-1 are markers associated, and correlated with the degree of atherosclerosis in normotensive type-2 diabetic patients.
Cell adhesion & migration 10/2009; 3(4):369-72. · 1.82 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Endothelial dysfunction, a common feature among hypertensive and type-2 diabetic patients, is associated with inflammation, increased levels of circulating soluble adhesion molecules (SAM), and urinary albumin excretion. The aim of this study was to evaluate the role of circulating SAM levels in the development of albuminuria in hypertensive type-2 diabetic patients.
We studied 30 hypertensive type-2 diabetic patients and 30 non-diabetic normotensive subjects, and measured their VCAM-1, ICAM-1 and E-selectin levels by ELISA, and their 24-hour urinary albumin excretion by nephelometry; the levels of circulating adhesion molecules and albuminuria were correlated with the Spearman correlation coefficient.
We found that the diabetic patients had significantly (p < 0.001) higher levels of circulating SAM than control subjects. When levels of circulating SAM were correlated with albuminuria, we found a significant correlation between VCAM-1 levels and 24-hour urinary albumin excretion (r = 0.4, p < 0.02).
Our results suggest that VCAM-1 may be a marker of nephropathy in hypertensive type-2 diabetic patients.
Kidney and Blood Pressure Research 04/2009; 32(2):106-9. · 1.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Endothelial dysfunction in hypertensive type-2 diabetic patients is associated with increased levels of circulating soluble adhesion molecules (SAM). SAM participate in the development of diabetic macroangiopathy and microangiopathy. The aim of this study was to compare the effect of trandolapril (T) and its fixed-dose combination with verapamil (FDTV) on SAM levels in hypertensive type-2 diabetic patients.
Forty type-2 diabetic patients with never-treated hypertension were randomly assigned to two groups. One group (FDTV) received 2/180 mg once a day; the other group received T 2 mg once a day. Study drugs were administered for three months in both groups. VCAM-1, ICAM, and E-selectin were measured by ELISA 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 ANOVA.
Both therapeutics regimens reduced significantly the levels of the SAM tested. When both groups were compared, we did not find a significant difference in ICAM and E-selectin reduction. However, VCAM-1 presented a significantly greater reduction (p = 0.022) in the trandolapril-verapamil group. No patient suffered adverse events.
Our results show that FDTV produces a greater reduction of VCAM-1 circulating levels than trandolapril alone. This may explain some of the beneficial effects of this fixed dosed combination that are non-related to its antihypertensive effects.
Clinical and Experimental Hypertension 11/2008; 30(7):682-8. · 1.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Endothelial dysfunction is a common feature in type 2 diabetic patients and is associated with inflammation, increased levels of circulating soluble adhesion molecules, and urinary albumin excretion. The aim of this study was to evaluate the role of circulating soluble adhesion molecules in the development of albuminuria.
Thirty normotensive type-2 diabetic patients and 30 non-diabetic normotensive subjects were studied. VCAM-1, ICAM-1, and E-selectin were measured by ELISA and 24-h urinary albumin excretion was also measured (nephelometry). Relationships between the levels of circulating adhesion molecules and albuminuria were examined with Spearman's correlation coefficient. Statistical analysis was performed with ANOVA.
It was found that diabetic patients have significantly (p<0.001) higher levels of circulating soluble adhesion molecules than control subjects. When levels of circulating soluble adhesion molecules were correlated with albuminuria, a significant correlation was found between VCAM-1 levels and 24-h urinary albumin excretion.
These results suggest that VCAM-1 may be a marker of nephropathy in normotensive type 2 diabetic patients.
Medical science monitor: international medical journal of experimental and clinical research 08/2007; 13(8):CR349-52. · 1.70 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This paper sought to determine if the fixed-dose combination of trandolapril and verapamil is effective in the treatment of hypertensive obese patients resistant to monotherapy. Thirty-six hypertensive obese patients uncontrolled by monotherapy were given the combination of trandolapril-verapamil (2/180 mg) for 12 weeks. Before and after taking the drug, they self-measured their blood pressure. Patients experienced a significant reduction of blood pressure (from 178 +/- 18/100 +/- 12 mm Hg to 135 +/- 14/76 +/- 7 mm Hg, p < 0.001). Eighty percent of patients reached therapeutic goals; one patient suffered from headaches and one had constipation. it was determined that the combination of trandolapril-verapamil is effective and safe for the management of hypertension in obese patients uncontrolled by monotherapy.
Clinical and Experimental Hypertension 10/2006; 28(7):619-24. · 1.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To compare the effect of fixed-dose trandolapril-verapamil (FDTV) with that of trandolapril on proteinuria in normotensive, type 2 diabetic patients.
A total of 60 normotensive, type 2 diabetic patients with 24-h proteinuria >300 mg were randomly assigned to two groups for open-label treatment. One group received 2 mg trandolapril/180 mg verapamil FDTV once daily; the other group received 2 mg trandolapril once daily. Study drugs were administered for 6 months in both groups. Creatinine clearance and 24-h urinary protein excretion were measured at the beginning and the end of the study. Patients were evaluated monthly for blood pressure, fasting blood glucose level, heart rate, and adverse events. Statistical analysis was performed using ANOVA.
Both groups experienced a statistically significant (P < 0.005) mean decrease in mean proteinuria from baseline: FDTV ([mean +/- SD] 1200 +/- 200 to 540 +/- 79 mg; P < 0.001) and trandolapril (1,105 +/- 212 to 750.9 +/- 134 mg; P < 0.005). A significantly greater reduction from baseline in proteinuria was observed in the FDTV group compared with the trandolapril group. Patients who received trandolapril experienced a statistically significant (P < 0.05) decrease in mean creatinine clearance (91.1 +/- 3.4 to 75.3 +/- 3 ml/min; P < 0.05) compared with patients who received FDTV (88.3 +/- 3.6 to 82.9 +/- 3.5 ml/min; P > 0.05). Final fasting blood glucose was significantly lower in the FDTV group (139 +/- 19) compared with the trandolapril group (154 +/- 22; P < 0.001). No significant differences were observed between the two groups in mean baseline or final measurements of blood pressure, mean heart rate, or frequency of adverse events.
Our results suggest that FDTV is more effective than trandolapril in reducing proteinuria in normotensive, type 2 diabetic patients. This effect on proteinuria is not related with blood pressure reduction.
Diabetes Care 08/2004; 27(7):1688-91. · 8.09 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Hypertension and type-2 diabetes affect endothelial function, which in turn increases the expression of soluble adhesion molecules and lead to the development of vascular damage. The aim of this study was to assess soluble adhesion molecule levels among normotensive and hypertensive diabetic patients.
Serum levels of soluble VCAM1, ICAM1 and e-selectin were measured in 80 type-2 diabetic patients, (40 normotensive and 40 hypertensive), and in 40 normotensive non-diabetic subjects by ELISA (RyDSystems Minneapolis). Statistical analysis was performed with ANOVA.
Among diabetic patients, levels of all three soluble adhesion molecules were significantly increased when compared with non-diabetic patients (p < 0.001 for all three molecules), In diabetic hypertensive patients, higher levels of ICAM1 were detected in comparison to normotensive diabetic patients (316 vs. 295 ng/ml p < 0.01), VCAM1 and e-selectin levels were not different between diabetic patients with and without hypertension.
Diabetes is associated with increased levels of soluble adhesion molecules, suggesting a role of these molecules may play in endothelial damage. ICAM1 is further increased when hypertension and diabetes are present. The latter may explain why diabetic-hypertensive patients displayed more complications than normotensive patients.
Gaceta medica de Mexico 144(1):11-4. · 0.22 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: both, the ankle-brachial index < 0.9, and microalbuminuria are considered markers of endothelial dysfunction. Our objective was to evaluate if there is a correlation between the ankle-brachial index (ABI) and the degree of albuminuria in diabetic normotensive patients.
we included 32 diabetic normotensive patients and measured their ABI, and their 24-h urinary albumin excretion by nephelometry; the ABI and albuminuria were correlated with the Spearman correlation coefficient.
we did not find overall correlation between the ABI and albuminuria (r = 0.21, 95 % CI = -0.14-0.52, p = 0.12); However, when we measured the correlation of an ABI < 0.9 with any degree of albuminuria, we found a significant correlation (r = -0.32 ± 0.11, 95 % CI = 0.027 to -0.6, p = 0.03); and when the correlation of ABI with albuminuria > 300 mg, we also found a significant correlation (r = -0.45 ± 0.11, 95 % CI = -0.015 to -0.76, p = 0.3).
our results suggest that ABI < 0.9 is a useful marker to estimate microalbuminuria in diabetic normotensive patients.
Revista medica del Instituto Mexicano del Seguro Social 49(3):311-4.
-
[show abstract]
[hide abstract]
ABSTRACT: Beyond its metabolic effects, insulin has several actions on the vasculature. Under normal conditions, insulin maintains normal endothelial function, but in the presence of insulin resistance, insulin leads to endothelial dysfunction. Insulin releases nitric oxide, which promotes an antiatherosclerotic, antiinflamatory and vasodilated state. However, in presence of high levels of angiotensin II, insulin activates pathways that lead to atherosclerosis, vasoconstriction and inflammation. We will review the actions of insulin on the vascular system, and its interactions with other vasoactive mediators, such as angiotensin II and endothelin-1.
Revista medica del Instituto Mexicano del Seguro Social 49(6):581-4.
