Troglitazone lowers blood pressure and enhances insulin sensitivity in Watanabe heritable hyperlipidemic rabbits

Although an association has been demonstrated between insulin resistance and hypertension, the mechanism of this association is not clear. Clarification of this point is important in hyperinsulinemic Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model of familial hypercholesterolemia, as hypertension markedly stimulates atherosclerosis in WHHL rabbits. The purpose of the present study was to determine whether troglitazone, a new thiazolidinedione drug for insulin resistance, could reduce blood pressure (BP) by improving hyperinsulinemia in WHHL rabbits. The effects of troglitazone, administered as a food admixture (24 mg/day) for 6 months, on hyperinsulinemia and BP were examined in WHHL rabbits. Insulin sensitivity (IS) was measured by the minimal model method using an intravenous glucose tolerance test (IVGTT). Troglitazone significantly reduced fasting insulin levels and the area-under-the-curve of insulin IVGTT profiles, indicating improved hyperinsulinemia. Troglitazone also significantly increased IS and reduced BP and heart rate (HR). Due to a significant correlation between HR and BP, a covariance analysis was performed. When BP was considered as a covariance factor, the change in HR was significant in treated rabbits. However, when HR was considered as a covariance factor, the change in BP was not significant, suggesting that reduced BP may be partly associated with changes in the sympathetic nervous system activity. In conclusion, troglitazone increases insulin sensitivity and lowers blood pressure in WHHL rabbits. Due to its dual effects on insulin resistance and hypertension, troglitazone offers a new pharmacological approach for the treatment of insulin-resistance syndrome.