Rilmenidine normalizes fructose-induced insulin resistance and hypertension in rats.
OBJECTIVE
The aim of this study was to determine the effects of rilmenidine (an antihypertensive drug that lowers blood pressure by decreasing sympathetic outflow) in an animal model of hypertension associated with insulin resistance, i.e. rats fed on a high-fructose diet.


METHODS
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 rats in the F group, rilmenidine (1 mg/kg per day) was added to the drinking 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+/-8g versus 45+/-8g, P< 0.05), but was prevented by rilmenidine treatment (32+/-2g). Arterial systolic blood pressure was increased in F rats (162+/-2 versus 155+/-2 mmHg, P< 0.05), rilmenidine reduced this value 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 utilization was lower (10+/-1 versus 14+/-1.5 mg/min per kg; P< 0.05) and hepatic 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 totally 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.
Pénicaud
L
L
Laboratoire de Neurobiologie, Plasticité Tissulaire et Metabolisme Energetique, UPRESA 5018-UPS CNRS, IFR Louis Bugnard, Toulouse, France.
Berthault
M F
MF
Morin
J
J
Dubar
M
M
Ktorza
A
A
Ferre
P
P
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects; D005632:Fructose / Q000494:pharmacology*; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology*; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008297:Male; D010080:Oxazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D000077769:Rilmenidine
D000959:Antihypertensive Agents; D001786:Blood Glucose; D008055:Lipids; D010080:Oxazoles; D005632:Fructose; D000077769:Rilmenidine