Long-term glucose infusion increases arterial pressure in dogs with cyclooxygenase-2 inhibition

A series of studies has shown that long-term infusion of insulin and glucos e does not increase mean arterial pressure (MAP) in dogs, but we have shown that the same infusion protocol or infusion of glucose alone increases art erial pressure in rats, This study tested the hypothesis that infusing gluc ose alone in dogs, with all insulin derived from endogenous secretion, woul d increase arterial pressure. Because fructose feeding in dogs also has bee n shown not to cause hypertension and because we have shown that prostaglan din production increases during insulin and glucose infusion, this study al so tested whether prostaglandins prevent the presser response in dogs. Dogs were instrumented and assigned in random crossover design to long-term cyc looxygenase-2 (COX-2) inhibition. After baseline measurements, glucose was infused in all dogs for 6 days (approximate to 500 g/d IV). Plasma insulin increased 3- to 4-fold and blood glucose increased significantly in both gr oups. The MAP (measured 24 h/d) response in control dogs was variable but o n average tended to increase, although not significantly. In the dogs with COX-2 inhibition, however, MAP increased significantly to a peak of 9+/-2 m m Hg and an average of 6+/-1 mm Hg above control. There was significant sod ium 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 fi rst study to report a long-term presser response with glucose infusion and hyperinsulinemia in dogs, and it suggests that the inability to detect this relationship previously was due to prostaglandins.