ABSTRACT
OBJECTIVE: Because autonomic dysfunction has been found to lead to cardiometabolic disorders and because studies have reported that simvastatin treatment has neuroprotective effects, the objective of the present study was to investigate the effects of simvastatin treatment on cardiovascular and autonomic changes in fructose-fed female rats. METHODS: Female Wistar rats were divided into three groups: controls (n=8), fructose (n=8), and fructose+ simvastatin (n=8). Fructose overload was induced by supplementing the drinking water with fructose (100 mg/L, 18 wks). Simvastatin treatment (5 mg/kg/day for 2 wks) was performed by gavage. The arterial pressure was recorded using a data acquisition system. Autonomic control was evaluated by pharmacological blockade. RESULTS: Fructose overload induced an increase in the fasting blood glucose and triglyceride levels and insulin resistance. The constant rate of glucose disappearance during the insulin intolerance test was reduced in the fructose group (3.4+ 0.32 percent/min) relative to that in the control group (4.4+ 0.29 percent/min). Fructose+simvastatin rats exhibited increased insulin sensitivity (5.4+0.66 percent/min). The fructose and fructose+simvastatin groups demonstrated an increase in the mean arterial pressure compared with controls rats (fructose: 124+2 mmHg and fructose+simvastatin: 126 + 3 mmHg vs. controls: 112 + 2 mmHg). The sympathetic effect was enhanced in the fructose group (73 + 7 bpm) compared with that in the control (48 + 7 bpm) and fructose+simvastatin groups (31+8 bpm). The vagal effect was increased in fructose+simvastatin animals (84 + 7 bpm) compared with that in control (49 + 9 bpm) and fructose animals (46+5 bpm). CONCLUSION: Simvastatin treatment improved insulin sensitivity and cardiac autonomic control in an experimental model of metabolic syndrome in female rats. These effects were independent of the improvements in the classical plasma lipid profile and of reductions in arterial pressure. These results support the hypothesis that statins reduce the cardiometabolic risk in females with metabolic syndrome.
Subject(s)
Animals , Female , Rats , Autonomic Nervous System/drug effects , Cardiovascular System/drug effects , Fructose/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Simvastatin/pharmacology , Blood Glucose/metabolism , Blood Pressure/drug effects , Blood Pressure/physiology , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/metabolism , Cardiovascular System/metabolism , Disease Models, Animal , Fasting/blood , Fructose/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/metabolism , Insulin Resistance/physiology , Metabolic Syndrome/drug therapy , Rats, Wistar , Simvastatin/metabolism , Time FactorsABSTRACT
A combinação de estatinas com niacina se apresenta como uma atraente associação, na presença de dislipidemia mista com níveis de HDL baixo, quando monoterapia é insuficiente para o alcance das metas lipídicas. Benefícios clínicos foram observados com a combinação de estatinas com niacina nos estudos FATS, HATS e ARBITER 2, mostrando atenuação no desenvolvimento da aterosclerose e/ou redução de eventos coronários, acompanhados de alterações lipídicas favoráveis. Em geral, esta combinação é bem tolerada. Recomenda-se monitoração adequada das enzimas hepáticas e muscular e, ainda, titulação cuidadosa de cada uma das drogas combinadas.