A large body of experimental and clinical evidence indicates that some AT1 receptor antagonists may have beneficial metabolic effects in addition to their well-known cardiovascular actions. Whether or not these metabolic effects are related to additional PPARγ agonist activity of some AT1 antagonists is still under debate. Therefore, the aim of the present study was to check the cardiovascular and metabolic effects of losartan lacking any PPAR agonist activity in a suitable experimental model of metabolic syndrome, namely SHHF rats (Spontaneously Hypertensive, Heart Failure). These rats exhibit obesity, hypertension, dyslipidemia and glucose intolerance. They lack leptin receptors. WKY and SH rats were considered as control of SHHF rats.

Losartan was delivered in the drinking water (10mg/kg/day during 3 months) to 12-week-old male rats. Cardiovascular and metabolic parameters were measured at the end of the treatment and compared to those of untreated SHHF rats at the same age. Intravenous glucose tolerance tests (IVGTT) were also performed. Total cholesterol, LDL, HDL, triglycerides and glucose were measured on plasma samples (0,5ml) taken from caudal veins. Blood pressure was measured (right femoral artery) under pentobarbital anaesthesia (60mg/kg, ip).

Mean values±SEM are presented. P values < 0.05 were considered significant. Unpaired Student¡¦s t-tests were used for intergroup comparisons.

Effects of a 3-month treatment are shown in the previous table (SHHF rats).

^* : p<0.05

Losartan impaired significantly glucose tolerance in SHHF rats.The treatment had no significant metabolic effect in WKY and SH rats.

Our study showed that, at an antihypertensive dose, losartan impaired glucose tolerance, fasted glycaemia, plasma triglycerides and free fatty acids in SHHF rats whereas it had no significant metabolic effect in WKY and SH rats.