Correlation between levels of circulating adipokines and adiponectin/resistin index with carotid intima-media thickness in hypertensive type 2 diabetic patients.

BACKGROUND: Hypoadiponectinemia and hyperresistinemia are associated with cardiovascular disease. The increase in the carotid intima-media thickness (CIMT) assessed by B-mode ultrasound has been directly associated with increased risk of myocardial infarction and stroke. OBJECTIVE: To evaluate the correlation between adipokine levels with CIMT in hypertensive type 2 diabetic patients. METHODS: Serum levels of adiponectin and resistin levels were measured by ELISA in 30 type 2 diabetic patients with never-treated hypertension and in age-matched healthy controls. The CIMT (B-mode color imaging of extracranial carotid arteries using high-resolution ultrasound) was also obtained. The relationship between adipokine levels and the adiponectin/resistin index with the CIMT was assessed by the Pearson correlation coefficient test. RESULTS: Adiponectin was lower (p < 0.05), and resistin higher (p < 0.01) in patients than in controls, CIMT correlated positively with resistin (R = 0.45, p < 0.02) and the adiponectin/resistin index (R = 0.58, p < 0.001), but not with adiponectin levels (r = -0.11, p > 0.1) in patients. Whereas only adiponectin levels correlated - negatively - with CIMT (r = -0.39, p < 0.02) in controls. CONCLUSION: Our results shown that the adiponectin/resistin index seems to be more strongly associated with atherosclerosis than adipokine levels, and may be used as a reliable marker of cardiovascular risk in type 2 diabetic hypertensive patients.

Beneficial effect of combination therapy using an angiotensin-converting enzyme inhibitor plus verapamil on circulating resistin levels in hypertensive patients with type 2 diabetes.

BACKGROUND: Resistin levels are strongly correlated with insulin resistance and vascular inflammation. Type 2 diabetic and hypertensive patients have higher circulating levels of resistin, which is associated with endothelial dysfunction. OBJECTIVE: To compare the effect of trandolapril (T) and its fixed-dose combination with verapamil (FDTV) on resistin levels in hypertensive, type-2 diabetic patients. METHODS: Forty type-2 diabetic patients with never-treated hypertension were randomly assigned to two groups. One group received FDTV 2 mg/180 mg once per day; the other group received T 2 mg once per day. Study drugs were administered for three months in both groups. Resistin levels were measured using ELISA at the beginning of the study and at study end. Patients were evaluated monthly for blood pressure, fasting serum glucose levels and adverse events. Statistical analysis was performed using ANOVA. RESULTS: All patients experienced a significant reduction in blood pressure. Both therapeutic regimens reduced resistin levels; however, FDTV treatment resulted in a greater decrease in resistin levels (mean [± SD] 25.5±13 ng/mL to 17.2±10 ng/mL) when compared with T treatment (22.4±12 ng/mL to 18.5±8 ng/mL) (P<0.05). None of the patients experienced an adverse event. CONCLUSION: Results showed that FDTV resulted in a greater reduction in resistin levels than T treatment alone.

Impact of trandolapril therapy and its combination with a calcium channel blocker on plasma adiponectin levels in patients with type 2 diabetes and hypertension.

INTRODUCTION: Adiponectin is secreted from adipose tissue and exhibits a protective effect against cardiovascular disease; plasma adiponectin concentrations are decreased in type 2 diabetic and in hypertensive patients. OBJECTIVE: The aim of this study was to compare the effect of trandolapril (T) and its fixed-dose combination with verapamil (FDTV) on adiponectin levels in hypertensive type 2 diabetic patients. METHODS: A total of 40 type 2 diabetic patients with never-treated hypertension were randomly assigned to two groups. One group received FDTV 180 mg + T 2 mg, once a day; the other group received T 2 mg once a day, administered for 3 months in both groups. Adiponectin was measured by enzyme-linked immunosorbent assay (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 analysis of variance (ANOVA). RESULTS: All patients experienced a significant reduction of blood pressure. Both therapeutics regimens increased the levels of adiponectin, However, FDTV produces a higher increase in the levels of the hormone (8.15 ± 4.6 to 10.96 ± 5.6 µg/ml) when compared with the T treatment (7.64 ± 3.8 to 8.92 ± 4.4 µg/ml), p < 0.05. None of the patients suffered adverse events. CONCLUSION: Our results show that the addition of FDTV to T produced a greater increase on adiponectin levels than trandolapril alone.

Correlation between circulating adhesion molecules and resistin levels in hypertensive type-2 diabetic patients.

BACKGROUND: Endothelial dysfunction, a common feature among hypertensive and type-2 diabetic patients, has been associated with inflammation and increased concentrations of serum soluble adhesion molecules and resistin, a monocyte-macrophage- and adipocyte-derived cytokine. THE AIM OF THIS STUDY: To determine if there is a correlation between the serum concentrations of ICAM-1, VCAM-1, Eselectin and resistin in hypertensive type-2 diabetic patients. METHODS: Thirty hypertensive type-2 diabetic patients were enrolled in the study. Serum ICAM-1, VCAM-1, E-selectin and resistin concentrations were determined by ELISA and correlated with the Spearman correlation coefficient. RESULTS: The patients' serum resistin concentrations significantly correlated with VCAM-1 (r = 0.31, p= 0.05) concentrations but not with ICAM-1 (r = 0.29, p = >0.05) and E-selectin (r = 0.10, p = 0.24) concentrations. CONCLUSION: VCAM-1 and resistin may participate in the pathophysiology of vascular damage in hypertensive type-2 diabetic patients. Serum resistin concentrations may be a marker of endothelial dysfunction.

[Participation of nitric oxide and arachidonic acid metabolites via cytochrome - P450 in the regulation of arterial blood pressure]. / Participación del óxido nítrico y los metabolitos del ácido araquidónico vía citocromo P450 en la regulación de la presión arterial.

Nitric oxide and cytochrome P450 arachidonic acid metabolites participate in blood pressure regulation. The synthesis of these autacoids leads to arterial hypertension. However, it is not known whether there is an interaction between them. Therefore, we studied the modulatory effect of nitric oxide and cytochrome P450-arachidonic acid metabolites, their interaction on blood pressure, and the renal content of cytochrome P450. Male Wistar rats were divided: 1) control, 2) L-NAME (100 mg/kg/d p.o.), 3) L-NAME + SnCl2 (10 mg/kg/d i.p.), and 4) L-NAME + dexamethasone (1 mg/kg/d s.c.). We measured blood pressure and collected urine and blood for nitric oxide measurement. NO2 was quantified by HPLC. Blood pressure was: control, 97 +/- 7 mmHg; L-NAME, 151 +/- 4.6 mmHg; L-NAME + SnCl2, 133 +/- 3 mmHg, and L-NAME + dexamethasone 152 +/- 4.5 mmHg. Urine nitrite concentration was: 1) 1.832 +/- 0.32, 2) 1.031 +/- 0.23, 3) 1.616 +/- 0.33, and 4) 1.244 +/- 0.33 mumol/mL, while the concentration in blood was: 1) 0.293 +/- 0.06, 2) 0.150 +/- 0.05, 3) 0.373 +/- 0.13, and 4) 0.373 +/- 0.07 mumol/mL. L-NAME + SnCl2 decreased cytochrome P450 renal content, and L-NAME + dexamethasone showed a similar response. In conclusion, both, nitric oxide and CYP-arachidonic acid metabolites play a role in the regulation of blood pressure. Nitric oxide also partially regulates renal cytochrome P450 content.

Participación del óxido nítrico y los metabolitos del ácido araquidónico vía citocromo P450 en la regulación de la presión arterial / Participation of nitric oxide and arachidonic acid metabolites via cytochrome-p450 in the regulation of arterial blood pressure

El óxido nítrico y los metabolitos del ácido araquidónico vía citocromo P450 contribuyen a la regulación de la presión arterial. La modificación en la síntesis de estos autacoides conduce a hipertensión arterial, sin embargo, se desconoce si existe interacción. Por ello, decidimos estudiar el papel modulador del óxido nítrico y los metabolitos del ácido araquidónico vía citocromo P450, y su interacción, sobre la presión arterial y el contenido renal de citocromo P450. Ratas Wistar macho fueron divididas por grupos: 1) Control, 2) L-NAME (100mg/kg/d v.o.), 3) L-NAME + SnCl2 (10mg/kg/d i.p.) y 4) L-NAME + dexametasona (1mg/kg/d s.c.). Se determinó la presión arterial sistólica y la concentración de nitritos por HPLC en orina y sangre. Los valores de presión arterial sistólica fueron: control 97 ± 7 mmHg, L-NAME 151 ± 4.6 mmHg, L-NAME + SnCl2 133 ± 3 mmHg, y L-NAME + dexametasona 152 ± 4.5 mmHg. Los nitritos en orina fueron: 1) 1.832 ± 0.32, 2) 1.031 ± 0.23, 3) 1.616 ± 0.33 y 4) 1.244 ± 0.33 μmol/mL y en sangre: 1) 0.293 ± 0.06, 2) 0.150 ± 0.05, 3) 0.373 ± 0.13 y 4) 0.373 ± 0.07 μmol/mL. El contenido renal de citocromo P450 fue abatido con el tratamiento de L-NAME + SnCl2, y una respuesta semejante se observó con L-NAME + dexametasona. Tanto óxido nítrico como los metabolitos del ácido araquidónico vía CYP participan en la regulación de la presión arterial. Además, el óxido nítrico contribuye regulando parcialmente el contenido renal del citocromo P450.

Nitric oxide and cytochrome P450 arachidonic acid metabolites participate in blood pressure regulation. The synthesis of these autacoids leads to arterial hypertension. However, it is not known whether there is an interaction between them. Therefore, we studied the modulatory effect of nitric oxide and cytochrome P450-arachidonic acid metabolites, their interaction on blood pressure, and the renal content of cytochrome P450. Male Wistar rats were divided: 1) control, 2) L-NAME (100 mg/kg/d p.o.), 3) L-NAME + SnCl2 (10 mg/kg/d i.p.), and 4) L-NAME + dexamethasone (1 mg/kg/d s.c.). We measured blood pressure and collected urine and blood for nitric oxide measurement. NO2 was quantified by HPLC. Blood pressure was: control, 97 ± 7 mmHg; L-NAME, 151 ± 4.6 mmHg; L-NAME + SnCl2, 133 ± 3 mmHg, and L-NAME + dexamethasone 152 ± 4.5 mmHg. Urine nitrite concentration was: 1) 1.832 ± 0.32, 2) 1.031 ± 0.23, 3) 1.616 ± 0.33, and 4) 1.244 ± 0.33 μmol/mL, while the concentration in blood was: 1) 0.293 ± 0.06, 2) 0.150 ± 0.05, 3) 0.373 ± 0.13, and 4) 0.373 ± 0.07 μmol/ mL. L-NAME + SnCl2 decreased cytochrome P450 renal content, and L-NAME + dexamethasone showed a similar response. In conclusion, both, nitric oxide and CYP-arachidonic acid metabolites play a role in the regulation of blood pressure. Nitric oxide also partially regulates renal cytochrome P450 content. (Arch Cardiol Mex 2003; 73:98-104).

Efectos vasculares de la trombina en arterias caninas y humana: su independencia del metabolismo del ácido araquidónico / Vascular effects of thrombin in the arteries in humans and dogs, independent of arachidonic acid metabolism

La trombina favorece la producción de postaciclina en células endoteliales, produce cambios en el tono vascular, estimula la liberación del factor relajante del endotelio, y potencia la respuesta del músculo liso vascular a varios agonistas. En este estudio se compararon los efectos vasculares de la trombina en arterias femoral y pulmonar caninas con los obtenidos en la arteria umbilical humana. Esto en presencia de inhibidores de cicloxigenasa y lipooxigenasa, beta antagonista, antagonista muscarínico, antiserotonina, antihistamínicos, alfa antagonista y un bloqueador de canales de calcio -además de heparina-, con y sin endotelio. Las concentraciones crecientes de trombina produjeron relajación y en arterias umbilicales se produjo contracción. La relajación fue dependiente del endotelio, mientras que la contracción no fue dependiente del endotelio. La relajación y contracción no fueron afectadas por inhibición del metabolismo del ácido araquidónico, ni por la presencia de los antagonistas utilizados. La heparina produjo en las arterias umbilicales una desviación de la curva dosis respuesta a trombina hacia la derecha y el bloqueador de canales de calcio produjo inhibición de esta contracción. En las arteria caninas la relación producida por trombina fue dependiente del endotelio, lo que haría pensar en un mediador endotelial. En arterias umbilicales la trombina produjo contracción en arterias con y sin endotelio por lo que se pensaría que esta respuesta no es producida por un factor endotelial. Parece estar mediada por un mecanismo que requiere de la unión de la trombina y la activación de entrada del calcio a las células.