CHRONIC INSULIN ADMINISTRATION ELEVATES BLOOD-PRESSURE IN RATS

To examine the relative contribution of dietary glucose and infused insulin on blood pressure, we administered a 4% glucose supplement (in drinking water) with and without insulin infusion (15.8 nmol [2.2 U]/d via osmotic minipump) to male Sprague-Dawley rats (n=6). We also tested the effect of the sympatholytic agent clonidine on rats receiving glucose and insulin. Blood pressure and heart rate were recorded via a novel radio telemetry system. Experiments were performed using a crossover design with three animals receiving treatment and three receiving vehicle for 10 days. After a 10-day washout period, the groups were reversed, and the experiment was repeated. Blood samples for insulin and glucose were drawn throughout the study. Systolic and diastolic blood pressures increased (by 6.0+/-1.2 and 2.2+/-1.3 mm Hg, respectively) in the animals given glucose alone in association with an increase in plasma insulin. However, blood pressure increased more rapidly and to a greater extent, systolic by 8.6+/-0.7 mm Hg and diastolic by 2.9+/-1.1 mm Hg, during the insulin treatment that raised plasma insulin above the levels observed during glucose feeding alone. Heart rate increased equally during both treatments. The average change in blood pressure and average plasma insulin during the infusion were correlated (r=.72, P=.009). Blood pressure dropped during the week following discontinuation of the insulin infusion. On rechallenge with insulin and glucose, blood pressure again rose and then decreased after termination of the insulin and glucose administration. Clonidine prevented the rise in blood pressure and heart rate. We conclude that modest dietary carbohydrate supplementation induces chronic hyperinsulinemia and elevated blood pressure in the rat. The blood pressure response is exaggerated by exogenous insulin administration and prevented by sympathetic blockade. These data suggest that hyperinsulinemia can contribute to a sympathetically mediated rise in blood pressure in normal rats.