Effect of telmisartan, angiotensin II receptor antagonist, on metabolic profile in fructose-induced hypertensive, hyperinsulinemic, hyperlipidemic rats

The metabolic syndrome (MS) is a common risk factor for cardiovascular disease and type-2 diabetes. Recently, telmisartan, an angiotensin II receptor antagonist that has an antihypertensive effect, has been reported to be a partial peroxisome proliferator-activated receptor γ (PPARγ) agonist. The anti-diabetic hormone adiponectin has been recognized as a marker of in vivo PPARγ activation. Therefore, we studied telmisartan's effect on the metabolic profile and adiponectin levels in a fructose-induced hypertensive, hyperinsulinemic, hyperlipidemic rat model. Twenty-four male Sprague-Dawley rats were divided into three groups (eight in each). One group of control rats was fed standard chow for 5 weeks while a second was fed a fructose-enriched diet. A third group was fed a fructose-enriched diet for 5 weeks and treated with telmisartan 5 mg/kg/day during the last 2 weeks. Fructose feeding increased systolic blood pressure (mean±SEM), from 130±1 to 148±2 mmHg, insulin from 0.26±0.03 to 0.68±0.08 ng/mL, and triglycerides from 102±6 to 285±23 mg/dL (p<0.05 for all variables). Telmisartan treatment reversed these effects and reduced blood pressure to 125±2 mmHg, insulin levels to 0.41±0.07 ng/mL, and triglycerides to 146±18 mg/dL (p<0.05 for all variables), while attenuating the increase in body weight during weeks 3 to 5. In contrast, telmisartan did not affect plasma adiponectin levels. In conclusion, although telmisartan is considered a partial PPARγ agonist, its beneficial effect in the fructose-induced hypertension, hypertriglyceridemia, and hyperinsulinemia rat model is apparently not mediated by adiponectin elevation but rather by direct inhibition of AT1 receptor.