Effect of an Insulin Sensitizer, Pioglitazone, on Hypertension in Fructose-Drinking Rats
Masami Suzuki, Chisako Nomura, Hiroyuki Odaka and Hitoshi Ikeda
Pharmaceutical Research Laboratories II, Pharmaceutical Research Division,
Takeda Chemical Industries Ltd., 2-17-85 Juso-Honmachi, Yodogawa-ku, Osaka
532, Japan
Abstract: To determine whether insulin resistance is responsible
for the development of hypertension, we examined whether blood pressure
changes in an insulin-resistant animal that was given a fructose solution
as their drinking water. Wistar Kyoto rats that drank a 10% fructose solution
for 10 weeks showed significant increases not only in plasma triglyceride
and insulin levels but also in systolic blood pressure. The decrease in
blood glucose in response to the intraperitoneal injection of insulin (0.2
- 1.0 U/kg) was slight in these fructose-drinking rats. To confirm whether
insulin resistance contributes to the observed hypertension, we examined
the effect of pioglitazone, an insulin sensitizer, on blood pressure in
rats given a 10% fructose solution. When pioglitazone was administered to
the rats at a dose of 10 mg/kg/day for 4 weeks from 12 weeks of age, plasma
triglyceride and insulin levels and systolic blood pressure decreased, and
blood glucose reduction in response to insulin was normalized. These results
suggest that insulin resistance is responsible for the development of hypertension
in fructose-drinking rats.
Keywords: Hypertension, Pioglitazone, Fructose, Insulin resistance, Hyperinsulinemia