EFFECTS OF RILMENIDINE IN RATS MADE RESIS TANT TO INSULIN AND HYPERTENSIVE BY A HIGH-FRUCTOSE DIET

This study was aimed to determine the effects of rilmenidine, an hypot ensive drug, in an animal model of hypertension associated with insuli n resistance, i.e. rats fed on a high fructose diet. Wistar rat were f ed during four weeks either on a standard Diet (S) or on a high fructo se diet (F 34.5% de fructose). In half of the 8 groups, rilmenidine (1 mg/kg/day) was added to the drinking water during the two last weeks of the diet (FR). Arterial blood pressure as well as insulin efficienc y were determined at the end of the four weeks. Body weight gain was h igher in F than in S rats (66+/-8 g versus 45+/-8 g; p <0.05), this wa s prevented by rilmenidine treatment (32+/-2g). Arterial systolic bloo d presure was increased in F rats (162+/-2 vs 155+/- 2 mmHg; p <0.05), rilmenidine brought this value back to normal (149+/-3 mmHg). During the euglycemic hyperinsulinemic clamp, glucose utilization was lower ( 10+/-1 vs 14+/-1.5 mg/min/kg; p <0.05) and hepatic glucose production higher (1+/-0.01 vs 0 mg/min/kg; p <0.01) in F than in S rats. These c hanges in insulin action were totally abolished by rilmenidine. These data demonstrate that rilmenidine can ameliorate the deleterious effec ts of a high fructose diet, i.e. weight gain, hypertension and resista nce to the effects of insulin Rilmenidine could represent a potential therapeutic agent for the treatment of hypertension associated with me tabolic disorders such as syndrom X and obesity.