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.