Long-Term Glucose Infusion Increases Arterial Pressure in Dogs With Cyclooxygenase-2 Inhibition

Abstract

A series of studies has shown that long-term infusion of insulin and glucose does not increase mean arterial pressure (MAP) in dogs, but we have shown that the same infusion protocol or infusion of glucose alone increases arterial pressure in rats. This study tested the hypothesis that infusing glucose alone in dogs, with all insulin derived from endogenous secretion, would increase arterial pressure. Because fructose feeding in dogs also has been shown not to cause hypertension and because we have shown that prostaglandin production increases during insulin and glucose infusion, this study also tested whether prostaglandins prevent the pressor response in dogs. Dogs were instrumented and assigned in random crossover design to long-term cyclooxygenase-2 (COX-2) inhibition. After baseline measurements, glucose was infused in all dogs for 6 days (≈500 g/d IV). Plasma insulin increased 3- to 4-fold and blood glucose increased significantly in both groups. The MAP (measured 24 h/d) response in control dogs was variable but on average tended to increase, although not significantly. In the dogs with COX-2 inhibition, however, MAP increased significantly to a peak of 9±2 mm Hg and an average of 6±1 mm Hg above control. There was significant sodium and volume retention during glucose infusion and a significant increase in glomerular filtration rate, but there were no between-group differences. Plasma renin activity increased only in the control group. This is the first study to report a long-term pressor response with glucose infusion and hyperinsulinemia in dogs, and it suggests that the inability to detect this relationship previously was due to prostaglandins.