Effect of sodium orthovanadate treatment on cardiovascular function in the hyperinsulinemic, insulin-resistant obese Zucker rat.

Abstract

We recently demonstrated that oral vanadate treatment ameliorates exaggerated vasoconstriction in aortic tissue from the hyperinsulinemic/insulin resistant obese Zucker rat. It has been suggested that changes in large artery contractility might contribute to the development of hypertension in this strain. Thus we examined the effect of vanadate treatment (0.5 mg/ml, p.o.) on conductance and resistance vessel function as well as blood pressure (BP) in Zucker rats. Vasoconstrictor responses to endothelin-1 (ET-1) and methoxamine and vasodilator responses to acetylcholine in the aorta and perfused mesenteric vascular bed served as indices of conductance and resistance function, respectively. Separate groups were treated with insulin (12 mU/kg/min, s.c.) to determine its role in the actions of vanadate. Vanadate treatment reduced (2.5-fold; p < 0.05) elevated plasma insulin levels and abolished exaggerated aortic vasoconstriction in obese rats. Vasoconstrictor responses in the mesenteric bed, however, were similar between obese and lean rats, and were unaffected by vanadate. Vanadate did not affect elevated BP in obese rats and actually increased BP in the lean group. Insulin treatment per se failed to affect vasomotor function or BP in either strain, and acetylcholine-evoked relaxation was similar in all groups. We conclude that whereas vanadate overcomes exaggerated central artery contractility in obese Zucker rats, it fails to affect resistance vessel function or BP in this strain, and might conversely elevate BP in normotensive lean control rats. The vascular actions of vanadate in obese rats appear to occur independent of changes in plasma insulin or endothelial function.