Hyperinsulinemia superimposed on insulin resistance does not elevate blood pressure

The role of hyperinsulinemia and insulin resistance in the development of hypertension is an area of much current interest. A central question that remains unanswered is whether exogenous hyperinsulinemia can elevate blood pressure (BP) in the presence of pre-existing insulin resistance. To examine this proposition, we studied the effects of chronic fructose feeding on plasma insulin levels and BP in insulin-resistant Zucker fatty rats and in lean (insulin-sensitive) controls. In addition, vascular responses to norepinephrine in aortae and mesenteric arteries were compared between groups. Zucker fatty rats were hyperinsulinemic, insulin-resistant, yet normotensive when compared with age-matched lean controls. Long term fructose feeding increased plasma insulin levels and BP in the lean group. Strikingly, the fatty rats remained refractory to fructose-induced increases in BP despite exaggeration of hyperinsulinemia. Vascular reactivity assessed in aortae and mesenteric arteries was comparable between groups. These data suggest that, in vivo, the mechanisms of hyperinsulinemia-induced hypertension are not operative in the face of pre-existing insulin resistance in obese Zucker rats