Potassium-induced increase in renal kallikrein secretion is attenuated in dissected renal connecting tubules of young spontaneously hypertensive rats

Abstract

It is suggested that attenuation of the renal kallikrein–kinin system (KKS) involved the development of hypertension in young spontaneously hypertensive rats (SHR). In the present study, a comparison was made between young SHR and Wistar Kyoto rats (WKY) to examine the ability to secrete renal kallikrein from the microdissected connecting tubules (CNT) by potassium or an ATP-sensitive potassium channel blocker, 4-morpholinecarboximidine- N-1-adamantyl- N′-cyclohexylhydrochloride (PNU-37883A), both of which are renal kallikrein secretagogues. Maximum effect of potassium on kallikrein secretion was observed 10 min after placing the tubules at concentration of 20 mM. Kallikrein secretion was also increased concentration-dependently by PNU-37883A (0.1, 1, 10, and 100 μM). In the presence of EDTA, NiCl 2, verapamil, xestspongin C (an inositol 1,4,5-trisphosphate (IP 3) receptor-selective antagonist), or ruthenium red (a ryanodine-sensitive receptor blocker), potassium-induced increase in renal kallikrein secretion was inhibited. Augmentation of renal kallikrein secretion by potassium or PNU-37883A was diminished in SHR compared to WKY. These results indicate that the ability to secrete renal kallikrein by potassium was attenuated in young SHR compared with WKY. Furthermore, it is suggested that the potassium-induced renal kallikrein secretion requires an extracellular Ca 2+ entry through Ca 2+ channels including L-type Ca 2+ channels and Ca 2+ release from intracellular Ca 2+ stores through IP 3 receptor and ryanodine receptor.