Bis(maltolato)Oxovanadium(IV) Attenuates Hyperinsulinemia and Hypertension in Spontaneously Hypertensive Rats

Abstract

We previously reported that bis(maltolato)oxovanadium(IV) (BMOV), an organic vanadium complex, decreased plasma insulin concentrations in nondiabetic rats without affecting plasma glucose levels (McNeill JH, Yuen VG, Hoveyda HR, Orvig C: Bis(maltolato)oxovanadium(IV) is a potent insulin mimic. J Med Chem 35:1489–1491, 1992). In this study, chronic oral BMOV treatment was started in 6-week-old spontaneously hypertensive (SH) rats and their Wistar-Kyoto (WKY) controls, and the effects of the drug on insulin sensitivity, plasma insulin, and blood pressure (BP) were studied. BMOV (0.35–0.45 mmol.kg−1.day−1) caused a sustained reduction in plasma insulin (198 ± 6 vs. untreated 366 ± 13.2 pM, P < 0.0001) and systolic BP (149 ± 3 vs. untreated 184 ± 3 mmHg, P < 0.0001) in SH rats. No changes were seen in WKY rats (plasma insulin: treated 228 ± 4.8 vs. untreated 222.6 ± 3.6 pM, P > 0.05; BP: treated 134 ± 3 vs. untreated 134 ± 5 mmHg, P > 0.05). At 13 weeks of age, euglycemic clamps were performed in fasted, conscious, mobile rats. During low-dose insulin infusions (14 pmol.kg−1 · min−1) with concomitant somatostatin administration, neither hepatic glucose output nor total body glucose uptake differed between the untreated SH and WKY rats. Insulin sensitivity, expressed as steady-state glucose clearance per unit of plasma insulin, was higher in the untreated SH compared with the untreated WKY rats (2.1 ± 0.2 vs. 1.2 ± 0.1 ml.kg−1.h−1.pM−1 P < 0.002). BMOV further enhanced insulin sensitivity in SH rats (3.6 ± 0.4, P < 0.002 vs. untreated SH rats). In conclusion, 1) SH rats are hyperinsulinemic but not insulin resistant compared with WKY rats; and 2) BMOV caused concurrent decreases in plasma insulin and BP in SH rats, which suggests that hyperinsulinemia may contribute toward the development of high BP in the SH rat.