Effects of KRN2391, a novel vasodilator, on pancreatic exocrine secretion in anesthetized dogs

The effects of KRN2391, a newly synthesized vasodilator, on pancreatic exocrine secretion in anesthetized dogs were compared with those of Ki3315, pinacidil and nitroprusside. Graded doses of KRN2391 (0.03-3 mumol/kg) and nitroprusside (0.003-0.3 mumol/kg) injected i.a. produced dose-dependent increases in the secretion of pancreatic juice, with a high concentration of protein and low concentration of bicarbonate, but Ki3315 or pinacidil did not (up to 10 mumol/kg). KRN2391 and nitroprusside increased the cyclic GMP levels in pancreatic tissue together with the increase in pancreatic secretion. Methylene blue decreased pancreatic secretion and cyclic GMP levels stimulated by KRN2391 and nitroprusside, but glibenclamide did not. KRN2391, Ki3315, pinacidil and nitroprusside caused vasodilator actions. These results suggest that KRN2391 has direct secretory properties on pancreatic exocrine glands of the dog and its nitro moiety has an important role in the stimulation of pancreatic secretion, but the K+ channel opening action or increasing of blood flow rate does not participate in the secretion.