VANADYL SULFATE PREVENTS FRUCTOSE-INDUCED HYPERINSULINEMIA AND HYPERTENSION IN RATS

To determine whether insulin resistance-and hyperinsulinemia are causally related to fructose-induced hypertension, we used vanadyl sulfate, a drug that improves insulin sensitivity in rats. Chronic oral vanadyl treatment was initiated in 6-week-old male Sprague-Dawley rats. One week after vanadyl was started, rats were fed either normal rat chow or a fructose-enriched diet. Plasma glucose and insulin levels and systolic blood pressure were measured weekly for 4 weeks. Fructose feeding induced hyperinsulinemia (fructose-fed, 366.6+/-8.4 versus control, 276+/-10.8 pmol/L, P<.001) and increased blood pressure (fructose-fed, 160+/-3.0 versus control, 124+/-3.0 mm Hg, P<.001). Vanadyl (0.4 to 0.6 mmol/kg per day) prevented the rise in plasma insulin (treated, 211.2+/-6.0 pmol/L, P<.001) and blood pressure (treated, 127+/-3.0 mm Hg, P<.001) in the fructose-fed rats without a change in plasma glucose. No change in blood pressure was seen in the control group. After 4 weeks, euglycemic clamps were performed on 20-hour fasted, conscious, mobile rats. Low-dose porcine insulin infusion (14 pmol/kg per minute) with concomitant somatostatin infusion resulted in similar steady-state plasma glucose and insulin levels in the various groups. Hepatic glucose production was suppressed and similar among various groups under clamp conditions. Insulin sensitivity index (micromoles of glucose per kilogram per hour per picomole per liter of insulin) was reduced in the fructose-fed rats compared with controls (fructose-fed, 0.9+/-0.4 versus control, 5.4+/-1.2, P<.002). Vanadyl caused a marked enhancement in the insulin sensitivity index in the fructose-fed rats (5.3+/-0.7), without any change in the control group (8.3+/-1.6, P>.05). Restoration of plasma insulin in the fructose-vanadyl-treated rats to pretreatment levels (daily subcutaneous Ultralente insulin, 14 000 pmol/kg per day) reversed the effects of vanadyl on blood pressure (vanadyl-treated plus insulin, 170+/-9.8 mm Hg), without a change in plasma glucose. We conclude that hyperinsulinemia, secondary to insulin resistance, may contribute to the development of fructose-induced hypertension and that vanadyl sulfate prevents fructose-induced increases in plasma insulin levels and blood pressure.