Troglitazone and metformin, but not glibenclamide, decrease blood pressurein Otsuka Long Evans Tokushima Fatty rats

To determine whether hypoglycemic agents such as sulfonylureas, biguanides and the newly developed insulin sensitizers such as troglitazone, have hypo tensive effects in an animal model of non-insulin-dependent diabetes mellit us associated with insulin resistance, male Otsuka Long Evans Tokushima Fat ty (OLETF) rats aged 12 weeks were administered following hypoglycemic agen ts or vehicle by gavage for 26 weeks; glibenclamide (5 mg/kg/day), metformi n (100 mg/kg/day) and troglitazone (70 mg/kg/day). The gain in body weight was similar in the different groups. At 36 weeks of age, troglitazone signi ficantly decreased fasting plasma glucose levels when compared to controls. The area under the curve (AUC) for insulin during glucose loading (2g/kg, i.p.) was 50% lower in the group treated with troglitazone. Serum triglycer ide levels in troglitazone-treated rats were also significantly lower than in the glibenclamide-treated group. Plasma membrane GLUT4 protein content w as significantly augmented by a factor of 1.48-fold (p<0.02) in the glibenc lamide-treated group and tended to be increased 1.32 times by administratio n of metformin(p=0.06). The systolic blood pressure increased with age in c ontrols and the glibenclamide-treated group. In contrast, treatment with ei ther metformin or troglitazone significantly decreased systolic blood press ure after the age of 29 weeks. Plasma norepinephrine and epinephrine concen trations did not show a significant decrease in the treated group when comp ared with the control group. These results suggest that metformin and trogl itazone, but not glibenclamide, lower blood pressure in an animal model of insulin resistance, providing further evidence of the beneficial effect of insulin sensitizing hypoglycemic agents on blood pressure.