RESUMEN
Metabolic syndrome (MetS) belongs to the serious health complications expanding in cardiovascular diseases, obesity, insulin resistance, and hyperglycemia. In this study, hypertriacylglycerolemic rats fed a high-fat-fructose diet (HFFD) were used as an experimental model of MetS to explore the effect of tested compounds. Effects of a new prospective pyridoindole derivative coded SMe1EC2 and the natural polyphenol rutin were tested. Endothelial nitric oxide synthase (NOS3) and nuclear factor kappa B (NF-?B) expression were assessed in the left ventricle immunohistochemically and left ventricle activity was monitored in isolated perfused rat hearts. NOS3 activity in the left ventricle decreased markedly as a result of a HFFD. NOS3 expression was upregulated by both substances. NF-?B expression was increased in the MetS group in comparison to control rats and the expression further increased in the SMe1EC2 treatment. This compound significantly improved the coronary flow in comparison to the control group during reperfusion of the heart followed after ischemia. Further, it tended to increase left ventricular systolic pressure, heart product, rate of maximal contraction and relaxation, and coronary flow during baseline assessment. Moreover, the compound SMe1EC2 decreased the sensitivity of hearts to electrically induced ventricular fibrillation. Contrary to this rutin decreased coronary flow in reperfusion. Present results suggest that despite upregulation of NOS3 by both substances tested, pyridoindole SMe1EC2 rather than rutin could be suitable in treatment strategies of cardiovascular disorders in MetS-like conditions.
Asunto(s)
Corazón/efectos de los fármacos , Indoles/uso terapéutico , Síndrome Metabólico/tratamiento farmacológico , Óxido Nítrico Sintasa de Tipo III/metabolismo , Piridinas/uso terapéutico , Rutina/uso terapéutico , Animales , Biometría , Evaluación Preclínica de Medicamentos , Fructosa/efectos adversos , Indoles/farmacología , Masculino , Síndrome Metabólico/enzimología , Síndrome Metabólico/etiología , Miocardio/metabolismo , FN-kappa B/metabolismo , Piridinas/farmacología , Ratas Wistar , Rutina/farmacologíaRESUMEN
OBJECTIVES: Aims of this study were to investigate the anti-arrhythmic and cardio-protective effect of atorvastatin and of a new pyridoindole derivative (SMe1EC2) on isolated and perfused hearts while following the Langendorff principles. BACKGROUND: Metabolic syndrome is a widely distributed condition progressing to cardiovascular disease. Many of the metabolic syndrome patients take (HMG)-co-enzyme A (CoA) reductase inhibitors with potential cardio-protective effects. SMe1EC2 is a promising new drug, exerting many positive effects in experimental settings. METHODS: Rats with induced metabolic syndrome were treated with atorvastatin (25 mg/kg) and SMe1EC2 (25 mg/kg and 0.5 mg/kg, respectively) daily for 3 weeks. After the treatment, the hearts were isolated and perfused according to Langendorff. RESULTS: Both atorvastatin and SMe1EC2 improved cardiac function by elevating the left ventricular developed pressure (VLDP) and cardiac contractility. Both SMe1EC2-treated groups improved LVDP during reperfusion, significantly increased âdP/dt, and moderately elevated +dP/dt values. The treatment with both atorvastatin and SMe1EC2 (25 mg/kg) significantly reduced malignant arrhythmia in comparison to control group and group treated with SMe1EC2 0.5 mg/kg. CONCLUSIONS: Owing to its anti-arrhythmic and cardio-protective effects, atorvastatin and SMe1EC2 could be of benefit to patients suffering from metabolic syndrome (Tab. 3, Fig. 3, Ref. 41).
Asunto(s)
Antiarrítmicos , Atorvastatina , Síndrome Metabólico , Daño por Reperfusión Miocárdica , Animales , Antiarrítmicos/farmacología , Atorvastatina/farmacología , Corazón , Humanos , Síndrome Metabólico/complicaciones , Daño por Reperfusión Miocárdica/complicaciones , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Ratas , Ratas WistarRESUMEN
OBJECTIVES: Metabolic disturbances are considered to condition the occurrence of malignant heart arrhythmias and negatively influence the chances of a patient to survive. To test this assumption, a model of metabolic syndrome was selected in which rats were receiving a diet resembling that of the westernized population. BACKGROUND: Metabolic syndrome is a comorbidity of major cardiovascular risk factors (dyslipidemia, hypertension, impaired glucose tolerance or insulin resistance, diabetes mellitus, and obesity), all facilitating cardiovascular complications leading to morbidity and mortality of patients. METHODS: Hearts were isolated and perfused according to Langendorff. Global ischemia was induced in the hearts and arrhythmia occurrence in reperfusion was monitored. All hearts were stimulated with the electro-cardio-stimulator to test the electrical inducibility of heart arrhythmia. RESULTS: Isolated hearts from rats with the metabolic syndrome were more susceptible to ventricular arrhythmias. The high-fat diet increased the occurrence of malignant heart arrhythmias in rats with metabolic syndrome to an even greater extent. All subjects with metabolic syndrome were sensitive to ventricular tachyarrhythmia with significantly decreased threshold to its induction in cardio-stimulation. CONCLUSIONS: These results indicate that metabolic syndrome patients may be more sensitive to the occurrence of malignant heart arrhythmias following myocardial infarction or other heart diseases (Tab. 1, Fig. 2, Ref. 34).
Asunto(s)
Dieta Alta en Grasa , Preparación de Corazón Aislado , Síndrome Metabólico/metabolismo , Isquemia Miocárdica/metabolismo , Fibrilación Ventricular/metabolismo , Animales , Arritmias Cardíacas/metabolismo , Susceptibilidad a Enfermedades , Masculino , Infarto del Miocardio , Ratas , Ratas Wistar , Factores de RiesgoRESUMEN
People with metabolic syndrome have higher risk of cardiovascular diseases then those without. The aim of the work was to investigate whether high fat diet administered to Prague hereditary hypertriglyceridemic (HTG) rats can induce signs of metabolic syndrome (MetS). Our results showed that HTG rats fed high fat diet (HTGch) had disturbed glucose metabolism and also lipid metabolism - increased serum triacylglycerols (TAG), total cholesterol (Ch), low-density lipoprotein-Ch (LDL-Ch), and decreased high-density lipoprotein-Ch (HDL-Ch). Their livers proved markers of developing steatosis. Moreover, HTGch had increased blood pressure, yet the vascular endothelium was not significantly damaged. All these changes were accompanied with oxidative stress and tissue damage identified as increased liver concentrations of thiobarbituric acid reactive substances (TBARS) and activity of the lysosomal enzyme N-acetyl-D-glucosaminidase (NAGA). We assume that the model used may be suitable for the study of MetS with no evidence of obesity. Prolongation of the high fat diet duration might have a major impact on all parameters tested, especially on vascular endothelial function.
Asunto(s)
Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Hipertrigliceridemia/sangre , Hipertrigliceridemia/etiología , Síndrome Metabólico/sangre , Síndrome Metabólico/etiología , Animales , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Masculino , Ratas , Ratas WistarRESUMEN
In cholesterol-fed rabbits the extent of monocyte involvement in atherogenesis may be influenced by the level of circulating leukocytes during hypercholesterolemia. We characterized the leukocytosis in rabbits fed either a 0.25% or a 0.1% cholesterol-enriched diet (0.25% or 0.1% rabbits, respectively). Circulating leukocytes were elevated by 1 week of feeding, and the elevation was sustained for at least 30 weeks. Differential counts were unchanged. Immature leukocytes were not seen, indicating that the leukocytosis was not due to premature release of bone marrow cells. Animals were free of bacterial or parasitic disease; selected rabbits with leukocytosis had normal body temperatures. Spleen weights averaged at least 100% higher in 0.25% rabbits but did not show histological evidence for hematopoiesis that could account for the leukocytosis. At approximately 22 weeks there was a second rise in leukocytosis in bilirubinemic 0.25% rabbits, suggesting that in the late stages of hypercholesterolemia, leukocytosis is related to liver failure. Cholesterol-fed rabbits also showed thrombocytosis. Existing leukocytosis and hypercholesterolemia were reversed to pretreatment levels by switching the rabbits to chow diets. In bone marrow from 0.25% rabbits, the mean number of cells per gram was greater (p less than 0.05) than that from normocholesterolemic rabbits. In 0.25% rabbits, the fraction of blood mononuclear cells showing phagocytosis of immunoglobulin G-coated red blood cells did not differ from that of controls, suggesting an unchanged population of these cells with regard to Fc and phagocytic function during hypercholesterolemia. These data suggest an effect (direct or indirect) of hypercholesterolemia on the production of leukocytes in the bone marrow and/or on the circulation kinetics of leukocytes in the blood.