Early increases in renal kallikrein secretion on administration of potassium or ATP-sensitive potassium channel blockers in rats

1 This study aimed to examine whether administration of potassium or ATP-se nsitive potassium channel (K-ATP channel) blockers caused early increases i n renal kallikrein (KK) secretion. To clarify this mechanism, the effect on renal KK secretion of a KATP channel blocker was compared with the effect resulting from use of an osmotic diuretic or volume load. Furthermore, the effect on potassium-induced increases in renal KK secretion by an additiona l treatment using a K-ATP channel blocker was examined. Lastly, the effect of a KATP channel blocker on renal KK secretion was also examined in superf used slices of kidney cortex. 2 Intravenous infusion of potassium augmented renal KK secretion within 30 min while urine volume increased gradually in both the potassium loading an d control groups. 3 Administration of the KATP channel blocker, 4-morpholinecarboximidine-N-1 -adamantyl-N-cyclohexylhydrochloride (PNU-37883A) or glibenclamide, caused a dose-dependent increase in renal KK secretion. 4 The concentration of KK in urine was higher in the PNU-37883A group as co mpared to the osmotic-diuretic or volume-load group. 5 PNU-37883A had no additive effect on the potassium-induced increase in re nal KK secretion. 6 Renal KK secretion increased in slices of kidney cortex incubated with PN U-37883A within 10 min of superfusion. 7 In conclusion, administration of both potassium and K-ATP channel blocker s induced early increases in renal KK secretion in the absence of the washo ut phenomenon. Potassium loading may have increased renal KK secretion thro ugh the same mechanism as the K-ATP channel blocker.