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 gamma (PPARgamma) agonist. The anti-diabetic hormone adiponectin has been recognized as a marker of in vivo PPARgamma 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 PPARgamma 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.
Kamari
Yehuda
Y
Hypertension Unit, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Israel.
Harari
Ayelet
A
Shaish
Aviv
A
Peleg
Edna
E
Sharabi
Yehonatan
Y
Harats
Dror
D
Grossman
Ehud
E
D052242:Adiponectin / Q000096:biosynthesis; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D004032:Diet; D005632:Fructose; D006946:Hyperinsulinism / Q000139:chemically induced* / Q000378:metabolism*; D006949:Hyperlipidemias / Q000139:chemically induced* / Q000378:metabolism*; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000139:chemically induced / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077333:Telmisartan; D014280:Triglycerides / Q000097:blood
D052242:Adiponectin; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D007328:Insulin; D014280:Triglycerides; D005632:Fructose; D000077333:Telmisartan