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