Acute effects of high ceiling diuretics on pancreatic blood flow and function

The possibility that a decrease in extracellular volume, induced by diuretics, would cause a decrease in pancreatic blood flow which, in turn, might compromise pancreatic function was examined. Employing fasted anesthetized mongrel dogs, the acute effects of furosemide, a typical high ceiling diuretic, on pancreatic blood flow and plasma levels of insulin and glucose were examined. Furosemide was found to induce a decline in pancreatic blood flow which was similar in all regions of the pancreas and the decrease was antagonized when extracellular volume depletion was prevented by infusing saline at the same rate as urine flow. The decrease in blood flow was significantly correlated with cumulative volume loss. Plasma levels of insulin and glucose were, however, not significantly altered during the studies. To increase the likelihood of determining significant decreases in plasma levels of insulin, acute studies were repeated in dogs in which plasma levels of insulin were increased by a continuous infusion of glucose. Both furosemide and the structurally unrelated high ceiling diuretic, ethacrynic acid, caused a decrease in pancreatic blood flow which was similar in all regions of the pancreas. The cumulative volume loss observed with administration of either furosemide or ethacrynic acid was significantly correlated with the level of pancreatic blood flow observed. Plasma levels of insulin and glucose were not significantly altered. It can be concluded that high ceiling diuretic drugs such as furosemide and ethacrynic acid do produce a loss in volume which is correlated with a decrease in pancreatic blood flow, but decreases in pancreatic blood flow alone do not appear to be sufficient to produce overt changes in pancreatic function in acute studies.