Insulin resistance, hyperinsulinemia, and obesity-associated hypertension

Recent work to elucidate the cause of obesity-associated hypertension has focused on insulin resistance and hyperinsulinemia. A significant amount of epidemiologic and correlational evidence suggests a link between these factors and obesity-associated hypertension, and acute insulin infusion studies have revealed renal, neural, and cardiovascular effects of this hormone that, if maintained chronically, could cause hypertension. However, correlations and acute effects may not reliably predict a chronic cause-and-effect relationship, and the fundamental question of whether chronic increases in plasma insulin concentration per se can produce a sustained increase in arterial pressure has not been completely resolved. Recent studies designed to address this question directly have found no evidence of a hypertensive effect of insulin in normal dogs, or in dogs with a 70% reduction in kidney mass and given a high sodium intake. Chronic hyperinsulinemia also did not potentiate the presser effects of angiotensin II or norepinephrine. In fact, hyperinsulinemia caused significant reductions in total peripheral vascular resistance in dogs and a decrease in arterial pressure. Furthermore, induction of insulin resistance in dogs made obese by being fed a high-fat diet eliminated the decrease in peripheral vascular resistance during chronic insulin infusion but did not uncover a pressor effect of hyperinsulinemia. In contrast, insulin infusion for up to 7 days produced a sustained increase in arterial pressure in rats. Although the mechanism for this pressor response is unknown, these data indicate either that there are major species differences in the chronic blood pressure response to insulin or that specific, presently unknown, conditions must exist in order for insulin to raise blood pressure. Also, it is not clear whether humans respond more like rats or dogs with respect to blood pressure changes during chronic hyperinsulinemia. However, it is apparent that obesity hypertension is probably much too complex to be ascribed to insulin resistance and hyperinsulinemia alone.