DIFFERENTIAL-EFFECTS OF CROMAKALIM ON PANCREATIC VASCULAR-RESISTANCE AND INSULIN-SECRETION INVITRO

The effects of the potassium channel opener cromakalim on vascular resistance and insulin output were investigated in vitro within the same experimental preparation, the isolated rat pancreas perfused at a constant pressure with a physiological solution containing 8.3 mM glucose. Cromakalim induced a clear and concentration-dependent dilatory response of pancreatic vessels; the concentration-response curve obtained in the range of 10(-8)-10(-5) M had a sigmoidal shape with a linear part between 10(-7) and 10(-6) M. Cromakalim did not inhibit insulin release at these concentrations. These results differ from those obtained with diazoxide, which has been previously shown both to inhibit insulin secretion and induce vasodilatation of the pancreatic vascular bed in a similar range of concentrations (10(-6) - 10(-5) M). The data presented provide evidence for a selective effect of cromakalim on pancreatic vascular resistance. Our present and previous results support the view that cromakalim is effective on K+ channels of vascular smooth muscle that differ from the ATP-sensitive K+ channel opened by diazoxide in insulin-secreting B-cells.