Effect of prostaglandins on pancreatic circulation in anesthetized dogs

To assess the contribution of prostaglandins (PGs) to the maintenance of vascular tone and exocrine secretion in the pancreas, the effects of several products of arachidonic acid metabolism on the blood flow and flow rate of exocrine secretion were examined in the isolated blood perfused pancreas of the pentobarbital-anesthetized dog with and without pretreatment with the cyclooxygenase inhibitors, indomethacin (2 mg/kg i.v.) or sodium meclofenamate (10 mg/kg i.v.). Intra-arterial administration of PGE2, PGI2 and thromboxane B2 at doses of 30 to 300 ng/kg produced vasodilation and increased flow of blood to the pancreas. Injections of either PGF2 alpha, 30 to 300 ng/kg, or PGD2, 10 to 100 ng/kg, produced a biphasic effect, viz., transient vasoconstriction followed by a prolonged vasodilation. Administration of either indomethacin or sodium meclofenamate significantly reduced pancreatic blood flow (P less than .01). In animals pretreated with either of the cyclooxygenase inhibitors, the effect of PGE2, PGI2 or PGD2 to increase blood flow to the pancreas was prolonged in duration. Administration of either PGs, thromboxane B2 or cyclooxygenase inhibitors did not markedly alter the flow rate of exocrine pancreatic secretion. These data indicate that one or more products of arachidonic acid formed through the cyclooxygenase pathway contribute to the maintenance of pancreatic vascular bed in a dilated state.