VANADYL SULFATE LOWERS PLASMA-INSULIN AND BLOOD-PRESSURE IN SPONTANEOUSLY HYPERTENSIVE RATS

Spontaneously hypertensive rats (SHR) are hyperinsulinemic compared with their Wistar-Kyoto (WKY) controls. Since previous studies have demonstrated that vanadyl sulfate lowers insulin levels in nondiabetic rats, we used vanadyl to explore the relation between hyperinsulinemia and hypertension. In a prevention study, 5-week-old SHR and WKY rats were started on long-term vanadyl sulfate treatment. Vanadyl in doses of 0.4 to 0.6 mmol/kg per day lowered plasma insulin (252+/-22.8 versus 336+/-12.6 pmol/L, treated versus untreated, P<.01) and systolic blood pressure (158+/-2 versus 189+/-1 mm Hg, P<.001) in SHR without causing any change in plasma glucose. No changes were seen in the treated WKY rats. At 11 weeks of age, a group of untreated rats from the prevention study was started on vanadyl treatment as before. Again, vanadyl caused significant and sustained decreases in plasma insulin (264+/-12.6 versus 342+/-6.6 pmol/L, treated versus untreated, P<.001) and blood pressure (161+/-1 versus 188+/-1 mm Hg, P<.001) in SHR but had no effect in the normotensive WKY controls. Furthermore, restoration of plasma insulin in the vanadyl-treated SHR to pretreatment levels (subcutaneous insulin, 14 000 pmol/kg per day) reversed the effects of vanadyl on blood pressure (vanadyl with insulin, 190+/-3.0 mm Hg versus vanadyl without insulin, mm Hg, P<.001). Since vanadyl treatment resulted in decreased weight gain, treated SHR were compared with a corresponding pair-fed group. The pair-fed rats remained as hypertensive as the untreated group, thus excluding any contribution of weight loss toward the antihypertensive effects observed with vanadyl. These results support the notion that hyperinsulinemia may contribute to the development of high blood pressure in SHR.