RILMENIDINE NORMALIZES FRUCTOSE-INDUCED INSULIN-RESISTANCE AND HYPERTENSION IN RATS

Objective The aim of this study was to determine the effects of rilmen idine tan antihypertensive drug that lowers blood pressure by decreasi ng sympathetic outflow) in an animal model of hypertension associated with insulin resistance, i.e, rats fed on a high-fructose diet. Design Wistar rats were fed for 4 weeks either on a standard diet (S group) or on a high-fructose diet (F group; 34.5% fructose). In half of the r ats in the F group, rilmenidine (1 mg/kg per day) was added to the dri nking water for the last 2 weeks of the diet (FR group). Results Body weight gain was higher in the F than in the S rats (66 +/- 8 g versus 45 +/- 8 g, P < 0.05), but was prevented by rilmenidine treatment (32 +/- 2 g). Arteria[ systolic blood pressure was increased in 8 rats (16 2 +/- 2 versus 155 +/- 2 mmHg, P< 0.05), rilmenidine reduced this valu e to normal (149 +/- 3 mmHg). Glucose tolerance, glucose turnover rate , and insulin secretion were not modified by the diet or by the drug. However, during a euglycemic hyperinsulinemic clamp, glucose utilizati on was lower (10 +/- 1 versus 14 +/- 1.5 mg/min per kg; P< 0.05) and h epatic glucose production higher (1 +/- 0.01 versus 0 mg/min per kg, P < 0.01) in F than in S rats. These changes in insulin action were tota lly abolished by rilmenidine. Conclusions These data demonstrate that rilmenidine can ameliorate the deleterious effects of a high-fructose diet, i.e. weight gain, hypertension, and resistance to the effects of insulin. J Hypertens 16 (suppl 3):S45-S49 (C) 1998 Lippincott William s & Wilkins.